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WO2004048938A2 - Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators - Google Patents

Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators Download PDF

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Publication number
WO2004048938A2
WO2004048938A2 PCT/US2003/038193 US0338193W WO2004048938A2 WO 2004048938 A2 WO2004048938 A2 WO 2004048938A2 US 0338193 W US0338193 W US 0338193W WO 2004048938 A2 WO2004048938 A2 WO 2004048938A2
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Prior art keywords
soft tissue
cancer
tissue sarcoma
expression
gene
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PCT/US2003/038193
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French (fr)
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WO2004048938A3 (en
Inventor
Natasha Aziz
Wendy M. Ginsburg
Albert Zlotnik
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Protein Design Labs, Inc.
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Priority to AU2003298786A priority Critical patent/AU2003298786A1/en
Publication of WO2004048938A2 publication Critical patent/WO2004048938A2/en
Publication of WO2004048938A3 publication Critical patent/WO2004048938A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/136Screening for pharmacological compounds

Definitions

  • the invention relates to the identification of nucleic acid and protein expression profiles and nucleic acids, products, and antibodies thereto that are involved in soft tissue sarcomas; and to the use of such expression profiles and compositions in diagnosis and therapy of such cancers.
  • the invention further relates to methods for identifying and using agents and/or targets that modulate these cancers.
  • Soft-tissue sarcomas are rare, representing only about 1 percent of all cancer cases. According to the American Cancer Society, approximately 8,700 new cases of soft-tissue sarcoma are diagnosed each year in adults and children in the United States. The age-adjusted incidence is 2 cases per 100,000 persons. There is a slight male predominance, with a male to female ratio of 11 : 10. The age distribution in adult soft-tissue sarcoma studies is: ⁇ 40 years, 20.7% of patients; 40-60 years, 27.6% of patients; > 60 years, 51.7% of patients.
  • Fat tissue tissue at the back of the abdominal cavity. Fat tissue may also originate from other locations, usually in the arms, legs, or body cavities.
  • Rhabdomyosarcomas are malignant tumors that resemble developing skeletal muscle. These tumors most commonly grow in the arms or legs, but can also develop in the head or neck area, as well as the urinary and reproductive organs.
  • Synovial sarcomas are malignant tumors made up of cells that resemble the cells in joints. ("Synovial cells" line the joints.) However, synovial sarcomas do not necessarily arise in a joint, and the name is probably a misnomer, since the cancer cells are probably quite different from normal joint cells. Synovial sarcomas can arise in any location in the body, and they often appear in young adults.
  • Fibrosarcomas are cancer of the fibroblast-type cells in the body. Fibroblasts form scars and do other important connective functions. Fibrosarcomas often occur in tendons and ligaments (fibrous tissue), usually in the arms, legs, or trunk.
  • Fibrosarcomas are rare, accounting for fewer than 7% of primary malignant bone tumors.
  • the five- and ten-year survival rates after radical surgery have been reported at 28% and 21.8%, respectively.
  • Chondrosarcomas are tumors of cells that form cartilage. Chondrosarcomas account for approximately 14% of malignant bone tumors. The incidence is greatest in individuals between 30 and 60 years of age, and among males. The most frequent sites of chondrosarcomas include the pelvic bone, long bones, scapula, and ribs. Less frequent sites include bones of the hand and foot, the nose, the maxilla, and the base of the skull. At present, chondrosarcomas remain nearly totally refractory to chemotherapeutic efforts inasmuch as chondrosarcomas usually have a poor blood supply. Consequently, drugs given intravenously generally do not reach the tumor in concentrations that are high enough to be therapeutically effective.
  • Malignant Fibrous Histiocytomas occur most commonly in the extremities (70-75%, with lower extremities accounting for 59%) of cases), followed by the retroperitoneum. Tumors typically arise in deep fascia or skeletal muscle.
  • Leiomyosarcomas are malignant tumors that develop from smooth muscle
  • tissue can arise anywhere in the body but the uterus or gastrointestinal tract are two relatively common locations.
  • Soft tissue sarcomas occur with greater frequency in patients with von Recklinghausen's disease (neurofibromatosis), Gardner's syndrome, Werner's syndrome, tuberous sclerosis, basal cell nevus syndrome, and among Li-Fraumeni kindreds (p53 mutations).
  • the occurrences of bone tumors are also associated with hyperpara-thyroidism, chronic osteomyelitis, old bone infarct, osteochondromas, and enchondromas.
  • 1-tnmunosuppressed patients such as renal transplant recipients and persons with autoimmunodeficiency syndrome (AIDS) have a higher risk for soft tissue sarcomas.
  • AIDS autoimmunodeficiency syndrome
  • Soft-tissue sarcomas have been reported to originate in radiation fields following therapeutic radiation for a variety of solid tumors. Exposure to various chemicals in specific occupations or situations has been linked with the development of soft-tissue sarcoma. These include the phenoxy acetic acids (forestry and agriculture workers), chlorophenols (sawmill workers), Thorotrast (diagnostic x-ray technicians), vinyl chloride (individuals working with this gas, used in making plastics and as a refrigerant), and arsenic (vineyard workers).
  • Soft-tissue sarcomas have been reported after previous exposure to alkylating chemotherapeutic agents, most commonly after treatment of pediatric acute lymphocytic leukemia.
  • Reactive pseudosarcomatous proliferans non- neoplastic lesions that mimic sarcomas
  • nodular fascilitis infiltrative or pseudosarcomatous fascilitis
  • proliferative fascilitis proliferative myositis
  • myositis ossificans malignant giant cell tumor
  • malignant lymphoma of bone reticulum cell sarcoma
  • Ewing's tumor Ewing's sarcoma
  • Osteosarcoma osteoogenic sarcoma. Signs and symptoms of soft-tissue sarcoma depend, in large part, on the anatomic site of origin.
  • metastasis occurs, it can sometimes be cured with surgery, but at other times it can be a life-threatening problem.
  • bone and soft tissue tumors tend to involve contiguous tissue and muscle, and aggressively metastasize early to the lungs via the hematogenous route.
  • soft tissue sarcomas can spread to regional lymph nodes.
  • the prognosis for patients with adult soft tissue sarcomas depends on several factors, including the patient's age and the size, histologic grade, and stage of the tumor. Factors associated with a poorer prognosis include age older than 60 years of age, tumors larger than 5 centimeters, or high-grade histology. While low-grade tumors are usually curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and the presence of hemorrhage and necrosis) are associated with higher local treatment failure rates and increased metastatic potential.
  • Some histological subtypes such as rhabdomyosarcomas, synovial sarcomas, and malignant histiocytomas are considered poor prognosticators due to their high grade. If there is distant metastasis to the lymph nodes, lungs, or other bones, the prognosis is also lowered.
  • Standard treatment options include: Surgical excision, surgical excision with preoperative or postoperative radiation therapy, and if the tumor is unresectable, high- dose preoperative radiation therapy may be used, followed by surgical resection and postoperative radiation therapy.
  • the present invention provides compositions and methods for detecting or modulating soft tissue sarcoma associated sequences.
  • the invention provides a method of detecting a sarcoma cancer- associated transcript in a cell in a patient, the method comprising contacting a biological sample from the patient with a polynucleotide that selectively hybridized to a sequence at least 80% identical to a sequence as shown in Tables 1 A-l IC.
  • the biological sample is a tissue sample
  • the biological sample comprises isolated nucleic acids, such as mRNA.
  • the method further comprises the step of amplifying nucleic acids before the step of contacting the biological sample with the polynucleotide.
  • the polynucleotide comprises a sequence as shown in the Tables.
  • the polynucleotide can be labeled, e.g., with a fluorescent label and can be immobilized on a solid surface.
  • the patient is undergoing a therapeutic regimen to treat a disease associated with these sarcomas or the patient is suspected of having a sarcoma-associated disorder.
  • the invention comprises an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in the Tables.
  • the nucleic acid molecule can be labeled, e.g., with a fluorescent or radioactive label.
  • the invention provides an expression vector comprising an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in the Tables or a host cell comprising the expression vector.
  • the invention provides an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A-l IC.
  • the invention provides an antibody that specifically binds a polypeptide which is encoded by a nucleotide sequence of the Tables.
  • the antibody can be conjugated or fused to an effector component such as a fluorescent label, a toxin, or a radioisotope.
  • the antibody is an antibody fragment or a humanized antibody.
  • the invention provides a method of detecting a cell undergoing such a cancer in a biological sample from a patient, the method comprising contacting the biological sample with an antibody that specifically binds to a polypeptide encoded by a nucleotide sequence of Tables 1 A-l IC.
  • the antibody is further conjugated or fused to an effector component, e.g., a fluorescent label.
  • the invention provides a method of detecting antibodies specific to a sarcoma in a patient, the method comprising contacting a biological sample from the patient with a polypeptide which is encoded by a nucleotide sequence of Tables lA-llC.
  • the invention also provides a method of identifying a compound that modulates the activity of a sarcoma-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a polypeptide encoded by a nucleotide sequence of Tables 1 A-l IC; and (ii) detecting an increase or a decrease in the activity of the polypeptide.
  • the polypeptide is encoded by a nucleotide sequence of Tables 1A-1 IC.
  • the polypeptide is expressed in a cell.
  • the invention also provides a method of identifying a compound that modulates the sarcoma, the method comprising steps of: (i) contacting the compound with a cell undergoing such cancer; and (ii) detecting an increase or a decrease in the expression of a polypeptide encoded by a nucleotide sequence of the Tables.
  • the detecting step comprises hybridizing a nucleic acid sample from the cell with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in the Tables.
  • the method further comprises detecting an increase or decrease in the expression of a second sequence encoded by a nucleotide sequence of the Tables.
  • the invention provides a method of inhibiting neoplastic properties in a cell that expresses a polypeptide at least 80% identical to a sequence encoded by a nucleotide sequence of Tables 1A-1 IC, the method comprising the step of contacting the cell with a therapeutically effective amount of an inhibitor of the polypeptide.
  • the polypeptide is encoded by a nucleotide sequence of Tables 1A-1 IC.
  • the inhibitor is an antibody.
  • Tables 1A-1 IC provide nucleotide sequence of genes that exhibit changes in expression levels as a function of time in tissue involved in cancer compared to normal or unaffected tissue.
  • Table 1 A lists about 523 genes upregulated in chondrosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® (DNA microchip) array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 2A lists about 763 genes upregulated in dermatofibrosarcoma protuberans relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 3 A lists about 625 genes upregulated in fibrosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 4A lists about 906 genes upregulated in liposarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 5A lists about 595 genes upregulated in synovial sarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. Table 6A lists about 977 genes upregulated in rhabdomyosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP " array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 7 A lists about 973 genes upregulated in soft tissue sarcomas relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 8 A lists about 712 genes upregulated in soft tissue sarcomas relative to normal soft tissues (muscle, skin, bone, adipose tissue). These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 9A lists about 1078 genes upregulated in malignant fibrous histiocytoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
  • Table 10A lists about 501 genes upregulated in soft tissue sarcoma relative to normal body tissues that are likely to encode proteins amenable to modulation by small molecules, peptides, or antibodies. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP ® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. The protein products of these genes often contain one or more domains indicative of have oncogenic function or of transducing intracellular signals, or of being modulatable by small molecules, peptides, or antibodies (e.g.
  • Tables 1B-1 IB list the accession numbers for those Pkey's lacking UnigenelD's for tables 1 A - 11 A, respectively.
  • Tables 1B-1 IB list the accession numbers for those Pkey's lacking UnigenelD's for tables 1 A - 11 A, respectively.
  • Gene clusters were compiled using sequences derived from Genbank ESTs and mRNAs. These sequences were clustered based on sequence similarity using Clustering and Alignment Tools (DoubleTwist, Oakland California). The Genbank accession numbers for sequences comprising each cluster are listed in the "Accession" column.
  • Tables lC-1 IC list the genomic positioning for those Pkey's lacking Unigene ID's and accession numbers in tables 1 A-l 1 A, respectively. For each predicted exon, genomic sequence source used for prediction is also listed and cross-referenced. Nucleotide locations of each predicted exon are also listed.
  • the present invention provides novel methods for diagnosis and prognosis evaluation for soft tissue sarcomas cancer (sometimes referred to herein as sarcoma disorders or STSD), as well as methods for screening for compositions which modulate those cancers or similar disorders. Also provided are methods for treating these cancers and related conditions. In particular, identification of markers selectively expressed on these cancers allows for use of that expression in diagnostic, prognostic, or therapeutic methods. As such, the invention defines various compositions, e.g., nucleic acids, polypeptides, antibodies, and small molecule agonists/antagonists, which will be useful to selectively recognize those markers.
  • therapeutic methods may take the form of protein therapeutics which use the marker expression for selective localization or modulation of function (for those markers which have a causative disease effect), for vaccines, identification of binding partners, or antagonism, e.g., using antisense or RNAi.
  • the markers may be useful for molecular characterization of subsets of soft tissue sarcoma cancer or related diseases, which subsets may actually require very different treatments.
  • the markers may also be important in related diseases to the specific cancers, e.g., which affect similar tissues in non-malignant diseases, or have similar mechanisms of induction/maintenance. Metastatic processes or characteristics may also be targeted.
  • Diagnostic and prognostic uses are made available, e.g., to subset related but distinct diseases, or to determine treatment strategy.
  • the detection methods may be based upon nucleic acid, e.g., PCR or hybridization techniques, or protein, e.g., ELISA, imaging, IHC, etc.
  • the diagnosis may be qualitative or quantitative, and may detect increases or decreases in expression levels.
  • soft tissue sarcomas include, e.g., soft tissue tumors (e.g., fibrosarcoma, liposarcoma, leiomyosarcoma, histiocytoma, fibrohistiocytic sarcoma), smooth muscle tumors (e.g., rhabdomyoma, rhabdomyosarcoma) tumors of the blood and lymph vessels (e.g., angiosarcoma.
  • soft tissue tumors e.g., fibrosarcoma, liposarcoma, leiomyosarcoma, histiocytoma, fibrohistiocytic sarcoma
  • smooth muscle tumors e.g., rhabdomyoma, rhabdomyosarcoma
  • tumors of the blood and lymph vessels e.g., angiosarcoma.
  • lymphangiosarcoma Kaposi's sarcoma
  • perivascular tumors e.g., glomus tumors, hemangiopericytoma
  • synovial tumors e.g., mesothelioma
  • neural tumors e.g., neurofibroma, neurofibrosarcoma, malignant peripheral nerve sheath tumors, granular cell tumors, plexosarcoma, ganglioneuroblastoma, neuroepithelioma, extraskeletal Ewing's sarcoma, schwannoma, neuroma, ganglioneuroma
  • paraganglioma e.g., chondrosarcoma, osteosarcoma
  • pluripotential mesenchymal tumors epitheliod sarcomas, rhabdoid tumors, desmoplastic small cell tumors, and alveolar sarcomas.
  • epitheliod sarcomas r
  • Tables 1A-1 IC provide unigene cluster identification numbers for the nucleotide sequence of genes that exhibit increased or decreased expression in soft tissue sarcoma cancer samples.
  • the tables also provide an exemplar accession number that provides a nucleotide sequence that is part of the unigene cluster.
  • soft tissue sarcoma cancer protein or "soft tissue sarcoma cancer polynucleotide” refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 92%, 94%, 96%, 97%, 98%, or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a unigene cluster of Tables 1A-1 IC; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence of Tables 1A-11C, and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to an
  • a polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal.
  • primate e.g., human
  • rodent e.g., rat, mouse, hamster
  • a "soft tissue sarcoma cancer polypeptide” and a "soft tissue sarcoma cancer polynucleotide,” include both naturally occurring or recombinant forms.
  • a “full length” soft tissue sarcoma cancer protein or nucleic acid refers to a soft tissue sarcoma cancer polypeptide or polynucleotide sequence, or a variant thereof, that contains the elements normally contained in one or more naturally occurring, wild type soft tissue sarcoma cancer polynucleotide or polypeptide sequences.
  • the "full length” may be prior to, or after, various stages of post- translation processing or splicing, including alternative splicing.
  • Bio sample as used herein is a sample of biological tissue or fluid that contains nucleic acids or polypeptides, e.g., of a cancer protein. Such samples include, but are not limited to, tissue isolated from primates, e.g., humans, or rodents, e.g., mice, and rats. Biological samples may also include sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histologic purposes.
  • a biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish. Livestock and domestic animals are of interest.
  • Providing a biological sample means to obtain a biological sample for use in methods described in this invention. Most often, this will be done by removing a sample of cells from a mammal, such as a human or animal, but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose), or by performing the methods of the invention in vivo. Archival tissues, having treatment or outcome history, will be particularly useful.
  • nucleic acids or polypeptide sequences refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (e.g., about 70% identity, preferably 75%, 80%, 85%, 90%, 91%, 93%, 95%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site or the like).
  • sequences are then said to be “substantially identical.”
  • This definition also refers to, or may be applied to, the compliment of a test sequence.
  • the definition also includes sequences that have deletions and/or additions, as well as those that have substitutions.
  • the algorithms can account for gaps and the like.
  • identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
  • sequence comparison typically one sequence acts as a reference sequence, to which test sequences are compared.
  • test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence algorithm program parameters Preferably, default program parameters can be used, or alternative parameters can be designated.
  • sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.
  • a “comparison window”, as used herein, includes reference to a segment of one of the number of contiguous positions selected from the group consisting of from about 20-600, usually about 50-200, more usually about 100-150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.
  • Methods of alignment of sequences for comparison are well-known. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2:482-489, by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol.
  • HSPs high scoring sequence pairs
  • initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them.
  • the word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; ahyays > 0) and N (penalty score for mismatching residues; always ⁇ 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached.
  • the BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment.
  • the BLAST algorithm also performs a statistical analysis of the similarity between two sequences. See, e.g., Karlin and Altschul (1993) Proc. Nat'l Acad. Sci. USA 90:5873-5787.
  • One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance.
  • P(N) the smallest sum probability
  • a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.
  • Log values may be negative large numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc.
  • An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below.
  • a polypeptide is typically substantially identical to a second polypeptide, e.g., where the two peptides differ only by conservative substitutions.
  • Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below.
  • Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequences.
  • a "host cell” is a naturally occurring cell or a transformed cell that contains an expression vector and supports the replication or expression of the expression vector.
  • Host cells may be cultured cells, explants, cells in vivo, and the like.
  • Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or mammalian cells, e.g., CHO, HeLa, and the like (see, e.g., the American Type Culture Collection catalog).
  • isolated refers to material that is substantially or essentially free from components that normally accompany it as found in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein or nucleic acid that is the predominant species present in a preparation is substantially purified. In particular, an isolated nucleic acid is separated from some open reading frames that naturally flank the gene and encode proteins other than protein encoded by the gene.
  • purified in some embodiments denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel.
  • nucleic acid or protein is at least about 85% pure, more preferably at least 95% pure, and most preferably at least 99%) pure.
  • “Purify” or “purification” in other embodiments means removing at least one contaminant or component from the composition to be purified. In this sense, purification does not require that the purified compound be homogeneous, e.g., 100% pure.
  • polypeptide peptide
  • protein protein
  • amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers.
  • amino acid refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids.
  • Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, ⁇ -carboxyglutamate, and O-phosphoserine.
  • Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, e.g., an ⁇ carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid.
  • Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.
  • Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
  • Constantly modified variants applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode a given protein. For instance, the codons GCA, GCC, GCG, and GCU all encode the amino acid alanine. Thus, at a position where an alanine is specified by a codon, the codon can be altered to one of the corresponding codons described without altering the encoded polypeptide.
  • nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. In certain contexts each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally similar molecule. Accordingly, a silent variation of a nucleic acid which encodes a polypeptide is implicit in a described sequence with respect to the expression product, but not necessarily with respect to actual probe sequences.
  • amino acid sequences it will be recognized that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds, or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" particularly where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
  • conservative substitutions include for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M). See, e.g., Creighton (1984) Proteins: Structure and Molecular Properties Freeman).
  • Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization, see, e.g., Alberts, et al. (eds. 2001) Molecular Biology of the Cell (4th ed.) Garland; and Cantor and Schimmel (1980) Biophysical Chemistry Part I: The Conformation of Biological Macromolecules Freeman.
  • Primary structure refers to the amino acid sequence of a particular peptide.
  • “Secondary structure” refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains. Domains are portions of a polypeptide that form a compact unit of the polypeptide and are typically 25 to approximately 500 amino acids long.
  • Typical domains are made up of sections of lesser organization such as stretches of ⁇ -sheet and -helices.
  • Tetiary structure refers to the complete three dimensional structure of a polypeptide monomer.
  • Quaternary structure refers to the three dimensional structure formed, usually by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms.
  • Nucleic acid or “oligonucleotide” or “polynucleotide” or grammatical equivalents used herein means at least two nucleotides covalently linked together.
  • Oligonucleotides are typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50, or more nucleotides in length, up to about 100 nucleotides in length.
  • Nucleic acids and polynucleotides are polymers, including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10,000, etc.
  • a nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have at least one different linkage, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphophoroamidite linkages (see Eckstein (1992) Oligonucleotides and Analogues: A Practical Approach Oxford Univ. Press); and peptide nucleic acid backbones and linkages.
  • Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in US Patent Nos.
  • nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.
  • nucleic acid analogs including, e.g., phosphoramidate (Beaucage, et al. (1993) Tetrahedron 49:1925-1963 and references therein; Letsinger (1970) J. Org. Chem. 35:3800-3803; Sblul, et al. (1977) Eur. J. Biochem. 81 :579-589; Letsinger, et al. (1986) Nuc. Acids Res. 14:3487-499; Sawai, et al. (1984) Chem. Lett. 805, Letsinger, et al. (1988) J. Am. Chem. Soc. 110:4470- 4471; and Pauwels, et al.
  • PNA peptide nucleic acids
  • backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in at least two advantages.
  • the PNA backbone exhibits improved hybridization kinetics.
  • PNAs have larger changes in the melting temperature (T m ) for mismatched versus perfectly matched basepairs.
  • DNA and T m melting temperature
  • RNA typically exhibit a 2-4° C drop in T m for an internal mismatch.
  • the drop is closer to about 7-9° C.
  • hybridization of the bases attached to these backbones is relatively insensitive to salt concentration, h addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.
  • the nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence.
  • the depiction of a single strand also defines the sequence of the complementary strand; thus the sequences described herein also provide the complement of the sequence.
  • the nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc.
  • Transcript typically refers to a naturally occurring RNA, e.g., a pre-mRNA, hnRNA, or mRNA.
  • nucleoside includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides.
  • nucleoside includes non-naturally occurring analog structures. Thus, e.g., the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.
  • a “label” or a “detectable moiety” is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, physiological, chemical, or other physical means.
  • Useful labels include 32p s fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins which can be made detectable, e.g., by incorporating a radiolabel into the peptide or used to detect antibodies specifically reactive with the peptide.
  • the labels may be inco ⁇ orated into the soft tissue sarcoma cancer nucleic acids, proteins, and antibodies. Many methods known for conjugating the antibody to the label may be employed.
  • effector or “effector moiety” or “effector component” is a molecule that is bound (or linked, or conjugated), either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds, to an antibody.
  • the "effector” can be a variety of molecules including, e.g., detection moieties including radioactive compounds, fluorescent compounds, enzymes or substrates, tags such as epitope tags, toxins; activatable moieties, chemotherapeutic agents; chemoattractant or immunomodulating entities; lipases; antibiotics; or radioisotopes, e.g., emitting "hard” beta radiation.
  • a "labeled nucleic acid probe or oligonucleotide” is one that is bound, e.g., covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds to a label such that the presence of the probe may be detected by detecting the presence of the label bound to the probe.
  • method using high affinity interactions may achieve the same results where one of a pair of binding partners binds to the other, e.g., biotin, streptavidin.
  • nucleic acid probe or oligonucleotide is a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation.
  • a probe may include natural (e.g., A, C, G, or T) or modified bases (7-deazaguanosine, inosine, etc.).
  • the bases in a probe may be joined by a linkage other than a phosphodiester bond, preferably one that does not functionally interfere with hybridization.
  • probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
  • Probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions.
  • the probes are preferably directly labeled, e.g., with isotopes, chromophores, lumiphores, chromogens, or indirectly labeled, e.g., with biotin to which a streptavidin complex may later bind.
  • By assaying for the presence or absence of the probe one can detect the presence or absence of the select sequence or subsequence. Diagnosis or prognosis may be based at the genomic level, or at the level of RNA or protein expression.
  • recombinant when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein, or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified.
  • recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed, or not expressed.
  • nucleic acid By the term “recombinant nucleic acid” herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid, e.g., using polymerases and endonucleases, in a form not normally found in nature. In this manner, operable linkage of different sequences is achieved.
  • an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined are both considered recombinant for the purposes of this invention.
  • a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, e.g., using the in vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non- recombinantly, are still considered recombinant for the purposes of the invention.
  • a "recombinant protein” is a protein made using recombinant techniques, e.g., through the expression of a recombinant nucleic acid as depicted above.
  • heterologous when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature.
  • the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source.
  • a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
  • a “promoter” is defined as an array of nucleic acid control sequences that direct transcription of a nucleic acid.
  • a promoter includes necessary nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element.
  • a promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription.
  • a “constitutive” promoter is a promoter that is active under most environmental and developmental conditions.
  • An “inducible” promoter is a promoter that is active under environmental or developmental regulation.
  • operably linked refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.
  • a nucleic acid expression control sequence such as a promoter, or array of transcription factor binding sites
  • an "expression vector” is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell.
  • the expression vector can be part of a plasmid, virus, or nucleic acid fragment.
  • the expression vector includes a nucleic acid to be transcribed in operable linkage to a promoter.
  • stringent hybridization conditions refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to essentially no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in "Overview of principles of hybridization and the strategy of nucleic acid assays” in Tijssen (1993) Hybridization with Nucleic Probes (Laboratory Techniques in Biochemistry and Molecular Biology) (vol. 24) Elsevier.
  • stringent conditions are selected to be about 5-10° C lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength pH.
  • T m is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at T m , 50% of the probes are occupied at equilibrium).
  • Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C for short probes (e.g., 10-50 nucleotides) and at least about 60° C for long probes (e.g., greater than about 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization.
  • Exemplary stringent hybridization conditions can be as following: 50% formamide, 5x SSC, and 1% SDS, incubating at 42° C, or, 5x SSC, 1% SDS, incubating at 65° C, with wash in 0.2x SSC, and 0.1% SDS at 65° C.
  • a temperature of about 36° C is typical for low stringency amplification, although annealing temperatures may vary between about 32-48° C depending on primer length.
  • a temperature of about 62° C is typical, although high stringency annealing temperatures can range from about 50-65° C, depending on the primer length and specificity.
  • Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90-95° C for 30-120 sec, an annealing phase lasting 30-120 sec, and an extension phase of about 72° C for 1-2 min. Protocols and guidelines for low and high stringency amplification reactions are provided, e.g., in Innis, et al. (1990) PCR Protocols: A Guide to Methods and Applications, Academic Press, NY. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions.
  • Exemplary "moderately stringent hybridization conditions” include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37° C, and a wash in IX SSC at 45° C.
  • a positive hybridization is typically at least twice background.
  • Alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous references, e.g., Ausubel, et al. (eds. 1991 and supplements) Current Protocols in Molecular Biology Wiley.
  • a parameter that is indirectly or directly under the influence of the cancer protein e.g., a physiological, functional, physical, or chemical effect, such as the ability to increase or decrease soft tissue sarcoma cancer. It includes ligand binding activity; cell viability; cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis; and other characteristics of cancer cells.
  • “Functional effects” include in vitro, in vivo, and ex vivo activities.
  • determining the functional effect is meant assaying for a compound that increases or decreases a parameter that is indirectly or directly under the influence of a soft tissue sarcoma cancer protein sequence, e.g., physiological, functional, enzymatic, physical, or chemical effects.
  • Such functional effects can be measured, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility properties for the protein, measuring inducible markers or transcriptional activation of the cancer protein; measuring binding activity or binding assays, e.g., binding to antibodies or other ligands, and measuring growth, cellular proliferation, cell viability, cellular transformation, growth factor or serum dependence, tumor specific marker levels, invasiveness into Matrigel, tumor growth and metastasis in vivo, mRNA and protein expression, and other characteristics of cancer cells.
  • spectroscopic characteristics e.g., fluorescence, absorbance, refractive index
  • hydrodynamic e.g., shape
  • chromatographic, or solubility properties for the protein measuring inducible markers or transcriptional activation of the cancer protein
  • binding activity or binding assays e.g., binding to antibodies or other ligands
  • the functional effects can be evaluated by many means, e.g., microscopy for quantitative or qualitative measures of alterations in morphological features, measurement of RNA stability, identification of downstream or reporter gene expression (CAT, luciferase, ⁇ -gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, inducible markers, and ligand binding assays.
  • microscopy for quantitative or qualitative measures of alterations in morphological features
  • measurement of RNA stability identification of downstream or reporter gene expression (CAT, luciferase, ⁇ -gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, inducible markers, and ligand binding assays.
  • Inhibitors are used to refer to activating, inhibitory, or modulating molecules identified using in vitro and in vivo assays of cancer polynucleotide and polypeptide sequences.
  • Inhibitors are compounds that, e.g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of soft tissue sarcoma cancer proteins, e.g., antagonists.
  • Activators are compounds that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate soft tissue sarcoma cancer protein activity.
  • Inhibitors, activators, or modulators also include genetically modified versions of soft tissue sarcoma cancer proteins, e.g., versions with altered activity, as well as naturally occurring and synthetic ligands, antagonists, agonists, antibodies, small chemical molecules and the like.
  • Such assays for inhibitors and activators include, e.g., expressing the cancer protein in vitro, in cells, or cell membranes, applying putative modulator compounds, and then determining the functional effects on activity, as described above.
  • Activators and inhibitors of soft tissue sarcoma cancer can also be identified by incubating cancer cells with the test compound and determining increases or decreases in the expression of 1 or more soft tissue sarcoma cancer proteins, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more cancer proteins, such as soft tissue sarcoma cancer proteins comprising the sequences set out in the Tables.
  • 1 or more soft tissue sarcoma cancer proteins e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more cancer proteins, such as soft tissue sarcoma cancer proteins comprising the sequences set out in the Tables.
  • Samples or assays comprising soft tissue sarcoma cancer proteins that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of inhibition.
  • Control samples (untreated with inhibitors) are assigned a relative protein activity value of 100%. Inhibition of a polypeptide is achieved when the activity value relative to the control is about 80%, preferably 50%, more preferably 25-0% 0 .
  • Activation of a soft tissue sarcoma cancer polypeptide is achieved when the activity value relative to the control (untreated with activators) is 110%, more preferably 150%, more preferably about 200-500%) (e.g., two to five fold higher relative to the control), more preferably 1000-3000%) higher.
  • change in cell growth refers to a change in cell growth or proliferation characteristics in vitro or in vivo, such as cell viability, formation of foci, anchorage independence, semi-solid or soft agar growth, changes in contact inhibition and density limitation of growth, loss of growth factor or serum requirements, changes in cell morphology, gaining or losing immortalization, gaining or losing tumor specific markers, ability to form or suppress tumors when injected into suitable animal hosts, and/or immortalization of the cell. See, e.g., pp. 231-241 in Freshney (1994) Culture of Animal Cells a Manual of Basic Technique (2d ed.) Wiley-Liss. "Tumor cell” refers to precancerous, cancerous, and normal cells in a tumor.
  • “Cancer cells,” “transformed” cells or “transformation” in tissue culture refers to spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material.
  • transformation can arise from infection with a transforming virus and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation is associated with phenotypic changes, such as immortalization of cells, aberrant growth control, nonmorphological changes, and/or malignancy. See, Freshney (2001) Culture of Animal Cells: A Manual of Basic Technique (4th ed.) Wiley-Liss.
  • Antibody refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen.
  • the recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes.
  • Light chains are classified as either kappa or lambda.
  • Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.
  • the antigen-binding region of an antibody will be most critical in specificity and affinity of binding. See Paul (ed. 1999) Fundamental Immunology (4th ed.) Raven.
  • An exemplary immunoglobulin (antibody) structural unit comprises a tetramer.
  • Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light” (about 25 kD) and one "heavy” chain (about 50-70 kD).
  • the N-terminus of each chain defines a variable region of about 100-110 or more amino acids primarily responsible for antigen recognition.
  • the terms variable light chain (VjJ and variable heavy chain (VJJ) refer to these light and heavy chains respectively.
  • Antibodies exist, e.g., as intact immunoglobulins or as a number of well- characterized fragments produced by digestion with various peptidases.
  • pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab)'2, a dimer of Fab which itself is a light chain joined to Vjj-Cjjl by a disulfide bond.
  • the F(ab)'2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F(ab)'2 dimer into an Fab' monomer.
  • the Fab' monomer is essentially Fab with part of the hinge region. See Paul (ed.
  • antibody fragments are defined in terms of the digestion of an intact antibody, it will be appreciated that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology.
  • antibody also includes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (e.g., McCafferty, et al. (1990) Nature 348:552-554).
  • a “chimeric antibody” is an antibody molecule in which (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule wliich confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.
  • the expression levels of genes are determined in different patient samples for which diagnosis information is desired, to provide expression profiles.
  • An expression profile of a particular sample is essentially a "fingerprint" of the state of the sample; while two states may have a particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. That is, normal tissue may be distinguished from sarcoma disorder tissue.
  • sequences that are differentially expressed in cancer versus non-cancer tissue allows the use of this information in a number of ways. For example, a particular treatment regime may be evaluated: does a chemotherapeutic drug act to down-regulate soft tissue sarcoma cancer, and thus tumor growth or recurrence, in a particular patient. Alternatively, a treatment step may induce other markers which may be used as targets to destroy tumor cells. Similarly, diagnosis and treatment outcomes may be done or confirmed by comparing patient samples with the known expression profiles. Cancer tissue can be compared to non-cancerous conditions, or be analyzed to determine the stage of soft tissue sarcoma cancer in the tissue, or origin of primary tumor, e.g., metastasis from a remote primary site.
  • these gene expression profiles allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; e.g., screening can be done for drugs that suppress the cancer expression profile.
  • screening can be done for drugs that suppress the cancer expression profile.
  • biochips comprising sets of the important soft tissue sarcoma cancer genes, which can then be used in these screens.
  • These methods can also be done on the protein basis; that is, protein expression levels of the cancer proteins can be evaluated for diagnostic purposes or to screen candidate agents.
  • the cancer nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the cancer proteins (including antibodies and other modulators thereof) admimstered as therapeutic drugs.
  • soft tissue sarcoma cancer sequences include those that are up-regulated (e.g., expressed at a higher level) in disorders associated with soft tissue sarcoma cancer, as well as those that are down- regulated (e.g., expressed at a lower level).
  • the soft tissue sarcoma cancer sequences are from humans; however, as will be appreciated, soft tissue sarcoma cancer sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other soft tissue sarcoma cancer sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc) and pets (e.g., dogs, cats, etc.). Soft tissue sarcoma cancer sequences from other organisms may be obtained using the techniques outlined below.
  • Soft tissue sarcoma cancer sequences can include both nucleic acid and amino acid sequences.
  • the soft tissue sarcoma cancer sequences are recombinant nucleic acids. These nucleic acid sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes or PCR microtiter plates with selected probes to the soft tissue sarcoma cancer sequences.
  • a soft tissue sarcoma cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the sequences outlined herein.
  • the cancer screen typically includes comparing genes identified in different tissues, e.g., normal and cancer tissues, cancer and non-malignant conditions, non-malignant conditions and normal tissues, or tumor tissue samples from patients who have metastatic disease vs. non metastatic tissue.
  • Other suitable tissue comparisons include comparing cancer samples with metastatic cancer samples from other cancers, such as lung, stomach, gastrointestinal cancers, etc.
  • Samples of different stages of cancer e.g., survivor tissue, drug resistant states, and tissue undergoing metastasis, are applied to biochips comprising nucleic acid probes.
  • the samples are first microdissected, if applicable, and treated for the preparation of mRNA.
  • Suitable biochips are commercially available, e.g., from Affymetrix, Santa Clara, CA. Gene expression profiles as described herein are generated and the data analyzed.
  • the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, and not limited to lung, heart, brain, liver, stomach, kidney, muscle, colon, small intestine, large intestine, spleen, bone, and/or placenta, h another embodiment, those genes identified during the cancer screen that are expressed in a significant amount in other tissues (e.g., essential organs) are removed from the profile, although in some embodiments, this is not necessary (e.g., where organs may be dispensable, e.g., female or male specific). That is, when screening for drugs, it is usually preferable that the target expression be disease specific, to minimize possible side effects on other organs were there expression.
  • other tissues e.g., essential organs
  • soft tissue sarcoma cancer sequences are those that are up-regulated in soft tissue sarcoma cancer; that is, the expression of these genes is higher in the cancer tissue as compared to non-cancer or non-malignant tissue.
  • Upregulation as used herein often means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred.
  • Another embodiment is directed to sequences up-regulated in non-malignant conditions relative to normal. Uniformity among relevant samples is desired. Unigene cluster identification numbers and accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. GenBank is available, see, e.g., Benson, et al.
  • sequences are also available in other databases, e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ).
  • EMBL European Molecular Biology Laboratory
  • DDBJ DNA Database of Japan
  • the sequences may be derived from assembly of available sequences or be predicted from genomic DNA using exon prediction algorithms, such as FGENESH. See Salamov and Solovyev (2000) Genome Res. 10:516-522. In other situations, sequences have been derived from cloning and sequencing of isolated nucleic acids.
  • soft tissue sarcoma cancer sequences are those that are down-regulated in cancer; that is, the expression of these genes is lower compared to non-cancer tissue.
  • Down-regulation as used herein often means at least about a two-fold change, preferably at least about a three fold change, with at least about five- fold or higher being useful.
  • nucleic acid By the term “recombinant nucleic acid” herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid e.g., using polymerases and endonucleases, in a form not normally found in nature.
  • nucleic acid in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention.
  • nucleic acid once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, e.g., using the in vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention.
  • a "recombinant protein” is a protein made using recombinant techniques, e.g., through the expression of a recombinant nucleic acid as depicted above.
  • a recombinant protein is distinguished from naturally occurring protein by at least one or more characteristics.
  • the protein may be isolated or purified away from ' some or most of the proteins and compounds with which it is normally associated in its wild type host, and thus may be substantially pure.
  • An isolated protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, preferably constituting at least about 0.5%, more preferably at least about 5% by weight of the total protein in a given sample.
  • a substantially pure protein comprises at least about 75% by weiglit of the total protein, with at least about 80% being preferred, and at least about 90% being particularly preferred.
  • the definition includes the production of a soft tissue sarcoma cancer protein from one organism in a different organism or host cell.
  • the protein may be made at a significantly higher concentration than is normally seen, through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels.
  • the protein may be in a form not normally found in nature, as in the addition of an epitope tag or amino acid substitutions, insertions and deletions, as discussed below.
  • the soft tissue sarcoma cancer sequences are nucleic acids.
  • Soft tissue sarcoma cancer sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes to the cancer sequences can be generated.
  • diagnostic applications which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes to the cancer sequences can be generated.
  • biochips comprising nucleic acid probes to the cancer sequences can be generated.
  • nucleic acid or oligonucleotide or grammatical equivalents herein means at least two nucleotides covalently linked together.
  • a nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have alternate backbones, comprising, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphophoroamidite linkages (see Eckstein (1992) Oligonucleotides and Analogues: A Practical Approach, Oxford Univ. Press); and peptide nucleic acid backbones and linkages.
  • Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in US Patent Nos.
  • nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip.
  • Nucleic acid analogs may find use in the present invention.
  • mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.
  • Particularly useful are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs.
  • PNA peptide nucleic acids
  • These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages. First, the PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (T m ) for mismatched versus perfectly matched basepairs.
  • DNA and RNA typically exhibit a 2-4° C drop in T m for an internal mismatch.
  • the drop is closer to 7-9° C.
  • hybridization of the bases attached to these backbones is relatively insensitive to salt concentration.
  • PNAs are not degraded by cellular enzymes, and thus can be more stable.
  • the nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence.
  • the depiction of a single strand also defines the sequence of a complementary strand; thus the sequences described herein also provide the complement of the sequence.
  • the nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc.
  • nucleoside includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides.
  • nucleoside includes non-naturally occurring analog structures.
  • a soft tissue sarcoma cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the soft tissue sarcoma cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
  • the cancer screen typically includes comparing genes identified in cancer cells with genes identified in controls.
  • Samples of normal tissue and tissue associated with soft tissue sarcoma cancer are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated for the preparation of mRNA. Suitable biochips are commercially available, e.g., from Affymetrix. Gene expression profiles as described herein are generated and the data analyzed.
  • the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, but not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone, and placenta.
  • those genes identified during the cancer screen that are expressed in significant amount in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drugs, it is usually preferable that the target be disease specific, to minimize possible side effects.
  • soft tissue sarcoma cancer sequences are those that are up-regulated in soft tissue sarcoma cancer disorders; that is, the expression of these genes is higher in the disease tissue as compared to normal tissue.
  • Up-regulation means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred.
  • Accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. See, e.g., Benson, et al. (1998) Nuc. Acids Res. 26:1-7. Sequences are also available in other databases, e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ). In addition, most genes were found to be expressed in a limited amount or not at all in heart, brain, lung, liver, breast, kidney, prostate, small intestine, and spleen.
  • EMBL European Molecular Biology Laboratory
  • DDBJ DNA Database of Japan
  • soft tissue sarcoma cancer sequences are those that are down-regulated in the soft tissue sarcoma cancer disorder; that is, the expression of these genes is lower in cancer tissue as compared to normal tissue.
  • Down- regulation as used herein means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred.
  • the ability to identify genes that undergo changes in expression with time during soft tissue sarcoma cancer can additionally provide high-resolution, high- sensitivity datasets which can be used in the areas of diagnostics, therapeutics, drug development, biosensor development, and other related areas.
  • the expression profiles can be used in diagnostic or prognostic evaluation of patients with soft tissue sarcoma cancer-associated disease.
  • subcellular toxicological information can be generated to better direct drug structure and activity correlation. See Anderson (June 11-12, 1998) Pharmaceutical Proteomics: Targets, Mechanism, and Function, paper presented at the IBC Proteomics conference, Coronado, CA.
  • the present invention provides a database that includes at least one set of data assay data.
  • the data contained in the database is acquired , e.g., using array analysis either singly or in a library format.
  • the database can be in a form in which data can be maintained and transmitted, but is preferably an electronic database.
  • the electronic database of the invention can be maintained on an electronic device allowing for the storage of and access to the database, such as a personal computer, but is preferably distributed on a wide area network, such as the World Wide Web.
  • compositions and methods for identifying and/or quantitating the relative and/or absolute abundance of a variety of molecular and macromolecular species from a biological sample exhibiting soft tissue sarcoma cancer e.g., the identification of soft tissue sarcoma cancer-associated sequences described herein, provide an abundance of information, which can be correlated with pathological conditions, predisposition to disease, drug testing, therapeutic monitoring, gene-disease causal linkages, identification of correlates of immunity and physiological status, among others.
  • the data generated from the assays of the invention is suited for manual review and analysis, prior data processing using high-speed computers may be utilized.
  • US Patents 6,023,659 and 5,966,712 disclose a relational database system for storing biomolecular sequence information in a manner that allows sequences to be catalogued and searched according to one or more protein function hierarchies.
  • US Patent 5,953,727 discloses a relational database having sequence records containing information in a format that allows a collection of partial-length DNA sequences to be catalogued and searched according to association with one or more sequencing projects for obtaining full-length sequences from the collection of partial length sequences.
  • US Patent 5,706,498 discloses a gene database retrieval system for making a retrieval of a gene sequence similar to a sequence data item in a gene database based on the degree of similarity between a key sequence and a target sequence.
  • US Patent 5,538,897 discloses a method using mass spectroscopy fragmentation patterns of peptides to identify amino acid sequences in computer databases by comparison of predicted mass spectra with experimentally-derived mass spectra using a closeness-of-fit measure.
  • US Patent 5,926,818 discloses a multidimensional database comprising a functionality for multi-dimensional data analysis described as on-line analytical processing (OLAP), which entails the consolidation of projected and actual data according to more than one consolidation path or dimension.
  • OLAP on-line analytical processing
  • US Patent 5,295,261 reports a hybrid database structure in which the fields of each database record are divided into two classes, navigational and informational data, with navigational fields stored in a hierarchical topological map which can be viewed as a tree structure or as the merger of two or more such tree structures. See also Mount (2001) Bioinformatics: Sequence and Genome Analysis CSH Press, NY; Durbin, et al. (eds. 1999) Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids Cambridge Univ. Press; Baxevanis and Oeullette (eds.
  • the present invention provides a computer database comprising a computer and software for storing in computer-retrievable form assay data records cross- tabulated, e.g., with data specifying the source of the target-containing sample from which each sequence specificity record was obtained.
  • At least one of the sources of target-containing sample is from a control tissue sample known to be free of pathological disorders.
  • at least one of the sources is a known pathological tissue specimen, e.g., a neoplastic lesion or another tissue specimen to be analyzed for soft tissue sarcoma cancer
  • the assay records cross-tabulate one or more of the following parameters for each target species in a sample: (1) a unique identification code, which can include, e.g., a target molecular structure and/or characteristic separation coordinate (e.g., electrophoretic coordinates); (2) sample source; and (3) absolute and/or relative quantity of the target species present in the sample.
  • the invention also provides for the storage and retrieval of a collection of target data in a computer data storage apparatus, which can include magnetic disks, optical disks, magneto-optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic bubble memory devices, and other data storage devices, including CPU registers and on-CPU data storage arrays.
  • the target data records are stored as a bit pattern in an array of magnetic domains on a magnetizable medium or as an array of charge states or transistor gate states, such as an array of cells in a DRAM device (e.g., each cell comprised of a transistor and a charge storage area, which may be on the transistor).
  • the invention provides such storage devices, and computer systems built therewith, comprising a bit pattern encoding a protein expression fingerprint record comprising unique identifiers for at least 10 target data records cross-tabulated with target source.
  • the invention preferably provides a method for identifying related peptide or nucleic acid sequences, comprising performing a computerized comparison between a peptide or nucleic acid sequence assay record stored in or retrieved from a computer storage device or database and at least one other sequence.
  • the comparison can include a sequence analysis or comparison algorithm or computer program embodiment thereof (e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison may be of the relative amount of a peptide or nucleic acid sequence in a pool of sequences determined from a polypeptide or nucleic acid sample of a specimen.
  • the invention also may provide a magnetic disk, such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, AIX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing in a computerized sequence analysis, comparison, or relative quantitation method.
  • a magnetic disk such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, AIX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing in
  • the invention also provides a network, comprising a plurality of computing devices linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone line, ISDN line, wireless network, optical fiber, or other suitable signal transmission medium, whereby at least one network device (e.g., computer, disk array, etc.) comprises a pattern of magnetic domains (e.g., magnetic disk) and/or charge domains (e.g., an array of DRAM cells) composing a bit pattern encoding data acquired from an assay of the invention.
  • a network device e.g., computer, disk array, etc.
  • a pattern of magnetic domains e.g., magnetic disk
  • charge domains e.g., an array of DRAM cells
  • the invention also provides a method for transmitting assay data that includes generating an electronic signal on an electronic communications device, such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
  • an electronic communications device such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like
  • the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
  • the invention provides a computer system for comparing a query target to a database containing an array of data structures, such as an assay result obtained by the method of the invention, and ranking database targets based on the degree of identity and gap weight to the target data.
  • a central processor is initialized to load and execute the computer program for alignment and/or comparison of the assay results.
  • Data for a query target is entered into the central processor via an I/O device.
  • Execution of the computer program results in the central processor retrieving the assay data from the data file, which comprises a binary description of an assay result.
  • the target data or record and the computer program can be transfened to secondary memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or SDRAM).
  • Targets are ranked according to the degree of co ⁇ espondence between a selected assay characteristic (e.g., binding to a selected affinity moiety) and the same characteristic of the query target and results are output via an I/O device.
  • a central processor can be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000, SPARC, MIPS 4400, MIPS 10000, VAX, etc.);
  • a program can be a commercial or public domain molecular biology software package (e.g., UWGCG Sequence Analysis Software, Darwin);
  • a data file can be an optical or magnetic disk, a data server, a memory device (e.g., DRAM, SRAM, SGRAM, SDRAM, EPROM, bubble memory, flash memory, etc.);
  • an I/O device can be a terminal comprising a video display and a keyboard, a modem, an ISDN terminal adapter, an Ethernet port, a punched card reader, a magnetic strip reader, or other suitable I/O device.
  • the invention also provides the use of a computer system, such as that described above, which comprises: (1) a computer; (2) a stored bit pattern encoding a collection of peptide sequence specificity records obtained by the methods of the invention, which may be stored in the computer; (3) a comparison target, such as a query target; and (4) a program for alignment and comparison, typically with rank- ordering of comparison results on the basis of computed similarity values.
  • Soft tissue sarcoma cancer proteins of the present invention maybe classified as secreted proteins, transmembrane proteins, or intracellular proteins.
  • the soft tissue sarcoma cancer protein is an intracellular protein.
  • Intracellular proteins may be found in the cytoplasm and/or in the nucleus or associated with the intracellular side of the plasma membrane. Intracellular proteins are involved in all aspects of cellular function and replication (including, e.g., signaling pathways); abenant expression of such proteins often results in unregulated or disregulated cellular processes. See, e.g., Alberts, et al. (eds. 1994) Molecular Biology of the Cell (3d ed.) Garland.
  • intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity, and the like.
  • Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles.
  • Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner.
  • PTB domains which are distinct from SH2 domains, also bind tyrosine phosphorylated targets.
  • SH3 domains bind to proline-rich targets.
  • PH domains, tetratricopeptide repeats and WD domains have been shown to mediate protein-protein interactions.
  • Pfam protein families
  • Pfam protein families
  • the cancer sequences are transmembrane proteins.
  • Transmembrane proteins are molecules that span a phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular 5 domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles. For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains, h addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins. 0 Transmembrane proteins may contain from one to many transmembrane domains.
  • receptor tyrosine kinases For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/threonine protein kinases contain a single transmembrane domain.
  • various other proteins including channels and adenylyl cyclases contain numerous transmembrane domains.
  • Many important cell 5 surface receptors such as G protein coupled receptors (GPCRs) are classified as "seven transmembrane domain" proteins, as they contain 7 membrane spanning regions. Characteristics of transmembrane domains include approximately 20 consecutive hydrophobic amino acids that may be followed or flanked by charged amino acids.
  • transmembrane protein receptors include, but are not limited to the insulin receptor, insulin-like growth factor receptor, human growth hormone receptor, glucose transporters, transferrin receptor, epidermal growth factor receptor, low density lipoprotein receptor, epidermal growth factor receptor, leptin receptor, and interleukin receptors, e.g., IL-1 receptor, IL-2 receptor, etc.
  • extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains. conserveed structure and/or functions have been ascribed to different extracellular motifs. Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are found on receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF, and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, neurotrophic factors and the like.
  • Extracellular domains also bind to cell- associated molecules. In this respect, they mediate cell-cell interactions.
  • Cell- associated ligands can be tethered to the cell, e.g., via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins.
  • Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
  • Soft tissue sarcoma cancer proteins that are transmembrane are useful in the present invention as they are readily accessible targets for immunotherapeutics, as are described herein.
  • transmembrane proteins can be also useful in imaging modalities.
  • Antibodies may be used to label such readily accessible proteins in situ.
  • antibodies can also label intracellular proteins, in which case samples are typically permeabilized to provide access to intracellular proteins, hi addition, some membrane proteins can be processed to release a soluble protein, or to expose a residual fragment. Released soluble proteins may be useful diagnostic markers, processed residual protein fragments may be useful markers of neoplastic disease.
  • a transmembrane protein can be made soluble by removing transmembrane sequences, e.g., through recombinant methods. Furthermore, transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
  • the cancer proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway. Secreted proteins are involved in numerous physiological events; e.g., if circulating, they often serve to transmit signals to various other cell types.
  • Secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor), an endocrine manner (acting on cells at a distance, e.g., secretion into the blood stream), or exocrine (secretion, e.g., through a duct or to adjacent epithelial surface as sweat glands, sebaceous glands, pancreatic ducts, lacrimal glands, mammary glands, wax producing glands of the ear, etc.).
  • secreted molecules often find use in modulating or altering numerous aspects of physiology.
  • Soft tissue sarcoma cancer proteins that are secreted proteins are included in the present invention as they serve as good targets for diagnostic markers, e.g., for blood, plasma, serum, or stool tests. Those which are enzymes may be antibody or small molecule targets. Others may be useful as vaccine targets, e.g., via CTL mechanisms.
  • a soft tissue sarcoma cancer sequence is typically initially identified by substantial nucleic acid and/or amino acid sequence homology or linkage to the cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions. Typically, linked sequences on a mRNA are found on the same molecule.
  • percent identity can be determined using an algorithm such as BLAST.
  • One method utilizes the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.
  • Alignment may include the introduction of gaps in the sequences to be aligned.
  • the percentage of homology may be determined based on the number of homologous nucleosides in relation to the total number of nucleosides. Thus, e.g., homology of sequences shorter than those of the sequences identified will be determined using the number of nucleosides in the shorter sequence.
  • the nucleic acid homology is determined through hybridization studies.
  • nucleic acids which hybridize under high stringency to a nucleic acid of Tables 1 A-l IC, or its complement, or is also found on naturally occurring mRNAs is considered a soft tissue sarcoma cancer sequence.
  • less stringent hybridization conditions are used; e.g., moderate or low stringency conditions may be used; see Ausubel, supra, and Tijssen, supra.
  • the soft tissue sarcoma cancer nucleic acid sequences of the invention can be fragments of larger genes, e.g., they are nucleic acid segments. "Genes" in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, using the sequences provided herein, extended sequences, in either direction, of the cancer genes can be obtained, using techniques well known for cloning either longer sequences or the full length sequences; see Ausubel, et al., supra. Much can be done by informatics and many sequences can be clustered to include multiple sequences, e.g., systems such as UniGene.
  • the soft tissue sarcoma cancer nucleic acid Once the soft tissue sarcoma cancer nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire cancer nucleic acid coding regions or the entire mRNA sequence.
  • the recombinant cancer nucleic acid Once isolated from its natural source, e.g., contained within a plasmid or other vector or excised therefrom as a linear nucleic acid segment, the recombinant cancer nucleic acid can be further-used as a probe to identify and isolate other soft tissue sarcoma cancer nucleic acids, e.g., extended coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant cancer nucleic acids and proteins.
  • nucleic acid probes to the cancer nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, e.g., for gene therapy, vaccine, and/or antisense applications.
  • cancer nucleic acids that include coding regions of cancer proteins can be put into expression vectors for the expression of cancer proteins, again for screening purposes or for administration to a patient.
  • nucleic acid probes to soft tissue sarcoma cancer nucleic acids are made.
  • the nucleic acid probes attached to the biochip are designed to be substantially complementary to cancer nucleic acids, e.g., the target sequence (either the target sequence of the sample or to other probe sequences, e.g., in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs.
  • this complementarity need not be perfect; there may be a number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention.
  • the sequence is not a complementary target sequence.
  • substantially complementary herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under normal reaction conditions, particularly high stringency conditions, as outlined herein.
  • a nucleic acid probe is generally single stranded but can be partially single and partially double stranded.
  • the strandedness of the probe is dictated by the structure, composition, and properties of the target sequence.
  • the nucleic acid probes range from about 8-100 bases long, with from about 10-80 bases being prefened, and from about 30-50 bases being particularly prefened. That is, generally whole genes are not used. In some embodiments, much longer nucleic acids can be used, up to hundreds of bases.
  • more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That is, two, three, four, or more probes, with three being prefened, are used to build in a redundancy for a particular target.
  • the probes can be overlapping (e.g., have some sequence in common), or separate.
  • PCR primers may be used to amplify signal for higher sensitivity.
  • Nucleic acids can be attached or immobilized to a solid support in a wide variety of ways.
  • immobilized and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined.
  • the binding can typically be covalent or non-covalent.
  • non-covalent binding and grammatical equivalents herein is meant one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non- covalent binding of the biotinylated probe to the streptavidin.
  • covalent binding and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.
  • the probes are attached to the biochip in a wide variety of ways.
  • the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip.
  • the biochip comprises a suitable solid substrate.
  • substrate or “solid support” or other grammatical equivalents herein is meant a material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. Often, the substrate may contain discrete individual sites appropriate for individual partitioning and identification.
  • the number of possible substrates is very large, and includes, but is not limited to, glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc.
  • the substrates allow optical detection and do not appreciably fluoresce. See WO 00/55627.
  • the substrate is planar, although other configurations of substrates may be used as well.
  • the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume.
  • the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics.
  • the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two.
  • the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly prefened.
  • the probes can be attached using functional groups on the probes.
  • nucleic acids containing amino groups can be attached to surfaces comprising amino groups, e.g., using available linkers; e.g., homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200). h addition, in some cases, additional linkers, such as alkyl groups (including substituted and heteroalkyl groups) may be used.
  • oligonucleotides are synthesized, and then attached to the surface of the solid support. Either the 5' or 3' terminus may be attached to the solid support, or attachment may be via an internal nucleoside.
  • the immobilization to the solid support may be very strong, yet non-covalent.
  • biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
  • the oligonucleotides may be synthesized on the surface.
  • photoactivation techniques utilizing photopolymerization compounds and techniques are used.
  • the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO 95/35505; US Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the Affymetrix GENECHIP ® (DNA microchip anay) technology.
  • amplification-based assays are performed to measure the expression level of soft tissue sarcoma cancer-associated sequences. These assays are typically performed in conjunction with reverse transcription, h such assays, a soft tissue sarcoma cancer-associated nucleic acid sequence acts as a template in an amplification reaction (e.g., Polymerase Chain Reaction, or PCR). In a quantitative amplification, the amount of amplification product will be proportional to the amount of template in the original sample. Comparison to appropriate controls provides a measure of the amount of soft tissue sarcoma cancer-associated RNA. Methods of quantitative amplification are well known. Detailed protocols for quantitative PCR are provided, e.g., in Innis, et al. (1990) PCR Protocols: A Guide to Methods and Applications Academic Press.
  • a TAQMAN ® (reagents for nucleic acid amplification) based assay is used to measure expression.
  • TAQMAN ® based assays use a fluorogenic oligonucleotide probe that contains a 5' fluorescent dye and a 3' quenching agent. The probe hybridizes to a PCR product, but cannot itself be extended due to a blocking agent at the 3' end.
  • the 5' nuclease activity of the polymerase e.g., AMPLITAQ ® (enzyme for diagnostic applications), results in the cleavage of the TAQMAN ® probe.
  • ligase chain reaction LCR
  • Genomics 4:560-569 Landegren, et al. (1988) Science 241:1077-1080, and Barringer, et al. (1990) Gene 89:117-122
  • Barringer et al. (1990) Gene 89:117-122
  • transcription amplification Kwoh, et al. (1989) Proc. Nat'l Acad. Sci.
  • soft tissue sarcoma cancer nucleic acids e.g., encoding soft tissue sarcoma cancer proteins are used to make a variety of expression vectors to express cancer proteins which can then be used in screening assays, as described below.
  • Expression vectors and recombinant DNA technology are well known (see, e.g., Ausubel, supra, and Fernandez and Hoeffler (eds. 1999) Gene Expression Systems Academic Press) and are used to express proteins.
  • the expression vectors may be either self-replicating extrachromosomal vectors or vectors which integrate into a host genome.
  • control sequences refers to DNA sequences used for the expression of an operably linked coding sequence in a particular host organism. Control sequences that are suitable for prokaryotes, e.g., include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
  • Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence.
  • DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide;
  • a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or
  • a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.
  • "operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase.
  • Transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the soft tissue sarcoma cancer protein; e.g., transcriptional and translational regulatory nucleic acid sequences from Bacillus are preferably used to express the soft tissue sarcoma cancer protein in Bacillus. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known for a variety of host cells.
  • transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences.
  • the regulatory sequences include a promoter and transcriptional start and stop sequences.
  • Promoter sequences encode either constitutive or inducible promoters.
  • the promoters may be either naturally occurring promoters or hybrid promoters.
  • Hybrid promoters which combine elements of more than one promoter, are also known, and are useful in the present invention.
  • an expression vector may comprise additional elements.
  • the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, e.g., in mammalian or insect cells for expression and in a prokaryotic host for cloning and amplification.
  • the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct.
  • the integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are available. See, e.g., Fernandez and Hoeffler, supra; and Kitamura, et al. (1995) Proc. Nat'l Acad. Sci. USA 92:9146- 9150.
  • the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are available and will vary with the host cell used.
  • the soft tissue sarcoma cancer proteins of the present invention are produced by culturing a host cell transformed with an expression vector containing nucleic acid encoding a cancer protein, under the appropriate conditions to induce or cause expression of the cancer protein. Conditions appropriate for soft tissue sarcoma cancer protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained through routine experimentation or optimization. For example, the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction.
  • the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.
  • Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells.
  • yeast Of particular interest are Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells), THP1 cells (a macrophage cell line), and various other human cells and cell lines.
  • the soft tissue sarcoma cancer proteins are expressed in mammalian cells. Mammalian expression systems may be used, and include retroviral and adenoviral systems.
  • One expression vector system is a retroviral vector system such as is generally described in PCT/US97/01019 and PCT/US97/01048.
  • mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the S V40 early promoter, mouse mammary tumor virus LTR promoter, adenovims major late promoter, herpes simplex vims promoter, and the CMV promoter (see, e.g., Fernandez and Hoeffler, supra).
  • transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence.
  • transcription terminator and polyadenylation signals include those derived form SV40.
  • Methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, are available, and will vary with the host cell used. Techniques include dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei. h one embodiment, soft tissue sarcoma cancer proteins are expressed in bacterial systems. Promoters from bacteriophage may also be used. In addition, synthetic promoters and hybrid promoters are also useful; e.g., the tac promoter is a hybrid of the trp and lac promoter sequences.
  • a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable.
  • the expression vector may also include a signal peptide sequence that provides for secretion of the soft tissue sarcoma cancer protein in bacteria. The protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria).
  • the bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed.
  • Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin, and tetracycline. Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan, and leucine biosynthetic pathways. These components are assembled into expression vectors.
  • Expression vectors for bacteria include vectors for Bacillus subtilis, E. coli,
  • Streptococcus cremoris and Streptococcus lividans, among others (e.g., Fernandez and Hoeffler, supra).
  • the bacterial expression vectors are transformed into bacterial host cells using techniques such as calcium chloride treatment, electroporation, and others.
  • soft tissue sarcoma cancer proteins are produced in insect cells using, e.g., expression vectors for the transformation of insect cells, and in particular, baculovims-based expression vectors.
  • a soft tissue sarcoma cancer protein is produced in yeast cells.
  • Yeast expression systems include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yanowia lipolytica.
  • the soft tissue sarcoma cancer protein may also be made as a fusion protein, e.g., for the creation of monoclonal antibodies, if the desired epitope is small, the soft tissue sarcoma cancer protein may be fused to a carrier protein to form an immunogen. Alternatively, the soft tissue sarcoma cancer protein may be made as a fusion protein to increase expression, or for other reasons. For example, when the soft tissue sarcoma cancer protein is a peptide, the nucleic acid encoding the peptide may be linked to another nucleic acid for expression purposes. Fusion with detection epitope tags can be made, e.g., with FLAG, His6, myc, HA, etc.
  • the soft tissue sarcoma cancer protein is purified or isolated after expression.
  • Soft tissue sarcoma cancer proteins may be isolated or purified in a variety of ways depending on what other components are present in the sample and the requirements for purified product.
  • Standard purification methods include ammonium sulfate precipitations, electrophoretic, molecular, immunological, and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing.
  • the cancer protein may be purified using a standard anti-cancer protein antibody column. Ulfrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful.
  • the soft tissue sarcoma cancer proteins and nucleic acids are useful in a number of applications. They may be used as immunoselection reagents, as vaccine reagents, as screening agents, etc.
  • the soft tissue sarcoma cancer nucleic acids, proteins, and antibodies of the invention are labeled.
  • labeled herein is meant that a compound has at least one element, isotope, or chemical compound attached to enable the detection of the compound.
  • labels fall into three classes: a) isotopic labels, which may be radioactive or heavy isotopes; b) immune labels, which may be antibodies, antigens, or epitope tags; and c) colored or fluorescent dyes.
  • the labels may be inco ⁇ orated into the cancer nucleic acids, proteins, and antibodies.
  • the label should be capable of producing, either directly or indirectly, a detectable signal.
  • the detectable moiety may be a radioisotope, such as ⁇ H, ⁇ C, 32 , 35g 5 or 125i 5 a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta-galactosidase, or horseradish peroxidase.
  • Methods are known for conjugating the antibody to the label. See, e.g., Hunter, et al.
  • the present invention also provides soft tissue sarcoma cancer protein sequences.
  • a cancer protein of the present invention may be identified in several ways. "Protein” in this sense includes proteins, polypeptides, and peptides.
  • Nucleic acid sequences of the invention can be used to generate protein sequences, including cloning the entire gene and verifying its frame and amino acid sequence, or by comparing it to known sequences to search for homology to provide a frame, assuming the soft tissue sarcoma cancer protein has an identifiable motif or homology to some protein in the database being used.
  • the nucleic acid sequences are input into a program that will search all three frames for homology. This is done in an embodiment using the following NCBI Advanced BLAST parameters. The program is blastx or blastn.
  • the database is nr.
  • the input data is as "Sequence in FASTA format”.
  • the organism list is “none”.
  • the “expect” is 10; the filter is default.
  • the “descriptions” is 500, the “alignments” is 500, and the “alignment view” is pairwise.
  • the "Query Genetic Codes” is standard (1).
  • the matrix is BLOSUM62; gap existence cost is 11, per residue gap cost is 1 ; and the lambda ratio is .85 default. This results in the generation of a putative protein sequence.
  • Variants of of soft tissue sarcoma cancer-associated proteins are amino acid variants of the naturally occurring sequences, as determined herein.
  • the variants are preferably greater than about 75% homologous to the wild-type sequence, more preferably greater than about 80%, even more preferably greater than about 85%, and most preferably greater than 90%.
  • the homology will be as high as about 93-95 or 98%.
  • homology in this context means sequence similarity or identity, with identity being prefened.
  • Soft tissue sarcoma cancer proteins of the present invention may be shorter or longer than the wild type amino acid sequences.
  • included within the definition of soft tissue sarcoma cancer proteins are portions or fragments of the wild type sequences herein.
  • the soft tissue sarcoma cancer nucleic acids of the invention may be used to obtain additional coding regions, and thus additional protein sequence.
  • the soft tissue sarcoma cancer proteins are derivative or variant cancer proteins as compared to the wild-type sequence. That is, the derivative cancer peptide will often contain at least one amino acid substitution, deletion, or insertion, with amino acid substitutions being particularly useful at an appropriate position.
  • amino acid sequence variants typically fall into one or more of three classes: substitutional, insertional, or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the cancer protein, using cassette or PCR mutagenesis or other appropriate techniques, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above.
  • variant cancer protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis using established techniques.
  • Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the cancer protein amino acid sequence.
  • the variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics.
  • the mutation per se need not be predetermined.
  • random mutagenesis may be conducted at the target codon or region and the expressed cancer variants screened for the optimal combination of desired activity.
  • Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, e.g., Ml 3 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of cancer protein activities. Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1-20 amino acids, although considerably larger insertions maybe tolerated.
  • Deletions range from about 1-20 residues, although in some cases deletions may be much larger. Substitutions, deletions, insertions or a combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. However, larger changes may be tolerated in certain circumstances. When small alterations in the characteristics of the cancer protein are desired, substitutions are generally made in accordance with the amino acid substitution chart described.
  • variants typically exhibit essentially the same qualitative biological activity and will elicit the same immune response as a naturally-occurring analog, although variants also are selected to modify the characteristics of cancer proteins as needed.
  • the variant may be designed such that a biological activity of the cancer protein is altered. For example, glycosylation sites may be added, altered, or removed.
  • substitutions that are less conservative than those provided in the definition of "conservative substitution".
  • substitutions may be made which more significantly affect: the stracture of the polypeptide backbone in the area of the alteration, e.g., the alpha-helical or beta-sheet stracture; the charge or hydrophobicity of the molecule at the target site; or the bulk of the side chain.
  • substitutions which in general are expected to produce the greatest changes in the polypeptide's properties are those in which (a) a hydrophilic sidechain, e.g., serine or threonine, is substituted for (or by) a hydrophobic sidechain, e.g., leucine, isoleucine, phenylalanine, valine, or alanine; (b) a cysteine or proline is substituted for (or by) another residue; (c) a residue having an electropositive side chain, e.g., lysine, arginine, or histidine, is substituted for (or by) an electronegative side chain, e.g., glutamic or aspartic acid; (d) a residue having a bulky side chain, e.g., phenylalanine, is substituted for (or by) one not having a side chain, e.g., glycine; or (e) a proline residue is inco ⁇ orated or substitute
  • the variants typically exhibit a similar qualitative biological activity and will elicit the same immune response as the naturally-occurring analog, although variants also are selected to modify the characteristics of the soft tissue sarcoma cancer proteins as needed.
  • the variant may be designed such that the biological activity of the cancer protein is altered. For example, glycosylation sites may be altered or removed.
  • Covalent modifications of these cancer polypeptides are included within the scope of this invention.
  • One type of covalent modification includes reacting targeted amino acid residues of a cancer polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a cancer polypeptide.
  • Derivatization with bifunctional agents is useful, e.g., for crosslinking cancer polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-cancer polypeptide antibodies or screening assays.
  • Commonly used crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2- phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, e.g., esters with 4- azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis- N-maleimido- 1,8 -octane and agents such as methyl-3-[(p- azidophenyl)dithio]propioimidate.
  • Another type of covalent modification of a cancer polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide.
  • "Altering the native glycosylation pattern" is intended for pu ⁇ oses herein to mean deleting one or more carbohydrate moieties found in native sequence cancer polypeptide, and/or adding one or more glycosylation sites that are not present in the native sequence cancer polypeptide.
  • Glycosylation patterns can be altered in many ways. Different cell types may be used to express cancer-associated sequences to exhibit different glycosylation patterns. Addition of glycosylation sites to soft tissue sarcoma cancer polypeptides may also be accomplished by altering the amino acid sequence thereof.
  • the alteration may be made, e.g., by the addition of, or substitution by, one or more serine or threonine residues to the native sequence cancer polypeptide (for O-linked glycosylation sites).
  • the soft tissue sarcoma cancer amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the cancer polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
  • Another means of increasing the number of carbohydrate moieties on the soft tissue sarcoma cancer polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. See, e.g., WO 87/05330; and pp. 259-306 in Aplin and Wriston (1981) CRC Crit. Rev. Biochem.
  • Removal of carbohydrate moieties present on the soft tissue sarcoma cancer polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are applicable. See, e.g., Sojar and Bahl (1987) Arch. Biochem. Biophys. 259:52-57; and Edge, et al. (1981) Anal. Biochem. 118:131-137. Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases. See, e.g., Thotakura, et al. (1987) Meth. Enzymol. 138:350-359.
  • Another type of covalent modification of soft tissue sarcoma cancer protein comprises linking the cancer polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in US Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192; or 4,179,337.
  • nonproteinaceous polymers e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes
  • Soft tissue sarcoma cancer polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising a cancer polypeptide fused to another, heterologous polypeptide or amino acid sequence.
  • such a chimeric molecule comprises a fusion of a cancer polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind.
  • the epitope tag is generally placed at the amino-or carboxyl-terminus of the soft tissue sarcoma cancer polypeptide. The presence of such epitope-tagged forms of a cancer polypeptide can be detected using an antibody against the tag polypeptide.
  • the epitope tag enables the soft tissue sarcoma cancer polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag.
  • the chimeric molecule may comprise a fusion of a cancer polypeptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule.
  • Various tag polypeptides and their respective antibodies are available.
  • Examples include poly-histidine (poly-his) or poly-l istidine-glycine (poly-his-gly) tags; HIS6, and metal chelation tags, the flu HA tag polypeptide and its antibody 12CA5 (Field, et al. (1988) Mol. Cell. Biol. 8:2159-2165); the c-myc tag and the 8F9, 3C7, 6E10, G4, B7, and 9E10 antibodies thereto (Evan, et al. (1985) Mol. Cell. Biol. 5:3610-3616); and the He ⁇ es Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky, et al. (1990) Protein Engineering 3:547-553).
  • poly-histidine poly-his
  • poly-l istidine-glycine poly-his-gly
  • tag polypeptides include the Flag-peptide (Hopp, et al. (1988) BioTechnology 6:1204-1210); the KT3 epitope peptide (Martin, et al. (1992) Science 255:192-194); tubulin epitope peptide (Skinner, et al. (1991) J. Biol. Chem. 266:15163-15166); and the T7 gene 10 protein peptide tag (Lutz-Freyermuth, et al. (1990) Proc. Nat'l Acad. Sci. USA 87:6393- 6397).
  • probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related cancer proteins from humans or other organisms.
  • Particularly useful probe and/or PCR primer sequences include unique areas of the soft tissue sarcoma cancer nucleic acid sequence.
  • PCR primers are from about 15-35 nucleotides in length, with from about 20-30 being prefened, and may contain inosine as needed. The conditions for the PCR reaction are well known. See, e.g., Innis, PCR Protocols, supra.
  • soft tissue sarcoma cancer proteins can be made that are longer than those encoded by the nucleic acids of the Tables, e.g., by the elucidation of extended sequences, the addition of epitope or purification tags, the addition of other fusion sequences, etc.
  • Soft tissue sarcoma cancer proteins may also be identified as being encoded by soft tissue sarcoma cancer nucleic acids.
  • soft tissue sarcoma cancer proteins are encoded by nucleic acids that will hybridize to the sequences of the sequence listings, or their complements, as outlined herein.
  • the soft tissue sarcoma cancer protein when the soft tissue sarcoma cancer protein is to be used to generate antibodies, e.g., for immunotherapy or immunodiagnosis, the soft tissue sarcoma cancer protein should share at least one epitope or determinant with the full length protein.
  • epitope or determinant herein is typically meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC.
  • antibodies made to a smaller, e.g., fragment of, cancer protein will be able to bind to the full-length protein, particularly linear epitopes.
  • the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross-reactivity.
  • the epitope is selected from a protein sequence set out in Tables 1 A-l IC. Methods of preparing polyclonal antibodies exist (e.g., Coligan, supra; and
  • Polyclonal antibodies can be raised in a mammal, e.g., by one or more injections of an immunizing agent and, if desired, an adjuvant.
  • the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections.
  • the immunizing agent may include a protein encoded by a nucleic acid of the figures or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized.
  • immunogenic proteins include but are not limited to keyhole limpet hemocyanin, semm albumin, bovine thyroglobulin, and soybean trypsin inhibitor.
  • adjuvants which may be employed include Freund's complete adjuvant and MPL- TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected without undue experimentation.
  • the antibodies may, alternatively, be monoclonal antibodies.
  • Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495-497.
  • a hybridoma method a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the lymphocytes may be immunized in vitro.
  • the immunizing agent will typically include a polypeptide encoded by a nucleic acid of Tables 1A-1 IC, or fragment thereof, or a fusion protein thereof.
  • peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired.
  • the lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (e.g., pp. 59-103 in Goding (1986) Monoclonal Antibodies: Principles and Practice Academic Press).
  • Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed.
  • the hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells.
  • a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells.
  • the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.
  • the antibodies are bispecific antibodies.
  • Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens or that have binding specificities for two epitopes on the same antigen.
  • one of the binding specificities is for a protein encoded by a nucleic acid Tables 1 A-l IC or a fragment thereof, the other one is for another antigen, and preferably for a cell-surface protein or receptor or receptor subunit, preferably one that is tumor specific.
  • tetramer-type technology may create multivalent reagents.
  • the antibodies to soft tissue sarcoma cancer protein are capable of reducing or eliminating a biological function of a soft tissue sarcoma cancer protein, as is described below. That is, the addition of anti-soft tissue sarcoma cancer protein antibodies (either polyclonal or preferably monoclonal) to cancer tissue may reduce or eliminate the neoplastic or malignant cancer activity. Generally, at least about 25% decrease in activity, growth, size or the like may be used, with at least about 50% being particularly useful and about 95-100% decrease being especially useful.
  • the antibodies to the soft tissue sarcoma cancer proteins are humanized antibodies (e.g., Xenerex Biosciences; Medarex, Inc.; Abgenix, Inc.; Protein Design Labs, Inc.).
  • Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non- human immunoglobulin.
  • Humanized antibodies include human immunoglobulins (recipient antibody) in which residues form a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity.
  • CDR complementary determining region
  • donor antibody such as mouse, rat or rabbit having the desired specificity, affinity and capacity.
  • Fv framework residues of the human immunoglobulin are replaced by conesponding non-human residues.
  • Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences.
  • a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions conespond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin consensus sequence.
  • the humanized antibody optimally also will typically comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones, et al. (1986) Nature 321:522-525; Riechmann, et al. (1988) Nature 332:323-329; and Presta (1992) Cun. Op. Struct. Biol. 2:593-596).
  • Humanization can be essentially performed following the method of Winter and co-workers (Jones, et al. (1986) Nature 321 :522- 525; Riechmann, et al. (1988) Nature 332:323-327; Verhoeyen, et al. (1988) Science 239:1534-1536), by substituting rodent CDRs or CDR sequences for conesponding sequences of a human antibody.
  • rodent CDRs or CDR sequences for conesponding sequences of a human antibody.
  • such humanized antibodies are chimeric antibodies (US Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by conesponding sequence from a non-human species.
  • Human-like antibodies can also be produced using phage display libraries (Hoogenboom and Winter (1992) J. Mol. Biol. 227:381-388; Marks, et al. (1991) J. Mol. Biol. 222:581-597) or human monoclonal antibodies (e.g., p. 77, Cole, et al. in Reisfeld and Sell (1985) Monoclonal Antibodies and Cancer Therapy Liss; and
  • human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in nearly all respects, including gene reareangement, assembly, and antibody repertoire. This approach is described, e.g., in US Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks, et al.
  • immunotherapy is meant treatment of soft tissue sarcoma cancer or related disease with an antibody raised against, e.g., proteins.
  • immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient).
  • Active immunization is the induction of antibody and/or T-cell responses in a recipient (patient).
  • Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised.
  • the antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen, leading to an immune response.
  • the soft tissue sarcoma cancer proteins against which antibodies are raised are secreted proteins as described above. Without being bound by theory, antibodies used for treatment may bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted cancer protein, e.g., in autocrine signaling.
  • the soft tissue sarcoma cancer protein to which antibodies are raised is a transmembrane protein.
  • antibodies used for treatment often bind the extracellular domain of the cancer protein and prevent it from binding to other proteins, such as circulating ligands or cell- associated molecules.
  • the antibody may cause down-regulation of the transmembrane cancer protein.
  • the antibody may be a competitive, non-competitive, or uncompetitive inhibitor of protein binding to the extracellular domain of the cancer protein.
  • the antibody may be an antagonist of the cancer protein.
  • the antibody prevents activation of the transmembrane cancer protein. In one aspect, when the antibody prevents the binding of other molecules to the cancer protein, the antibody prevents growth of the cell.
  • the antibody may also be used to target or sensitize the cell to cytotoxic agents, including, but not limited to TNF- ⁇ , TNF- ⁇ , IL- 1, INF- ⁇ , and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like.
  • cytotoxic agents including, but not limited to TNF- ⁇ , TNF- ⁇ , IL- 1, INF- ⁇ , and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like.
  • the antibody belongs to a sub-type that activates serum complement, or a similar effector function, when complexed with the transmembrane protein thereby mediating cytotoxicity or antigen-dependent cytotoxicity (ADCC).
  • ADCC antigen-dependent cytotoxicity
  • soft tissue sarcoma cancer is treated by administering to a patient antibodies directed against the transmembran
  • the antibody is conjugated or fused to an effector moiety.
  • the effector moiety can be a labeling moiety, e.g., a radioactive or fluorescent label, or a therapeutic moiety.
  • the therapeutic moiety is a small molecule that modulates the activity of the soft tissue sarcoma cancer protein.
  • the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the soft tissue sarcoma cancer protein.
  • the therapeutic moiety may inhibit enzymatic activity such as protease or collagenase activity associated with the cancer, or be an attractant of other cells, such as NK cells. See, e.g., Groh, et al. (2002) Nature 419:734-738.
  • the therapeutic moiety can also be a cytotoxic agent.
  • targeting the cytotoxic agent to soft tissue sarcoma cancer tissue or cells results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with cancer.
  • Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drags or toxins or active fragments of such toxins. Suitable toxins and their conesponding fragments include diphtheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin, and the like.
  • Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against soft tissue sarcoma cancer proteins, or binding of a radionuclide to a chelating agent that has been covalently attached to the antibody.
  • Targeting the therapeutic moiety to transmembrane cancer proteins not only serves to increase the local concentration of therapeutic moiety in the cancer afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.
  • the soft tissue sarcoma cancer protein against which the antibodies are raised is an intracellular protein.
  • the antibody may be conjugated or fused to a protein which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis.
  • a nucleic acid encoding the antibody is administered to the individual or cell.
  • an antibody thereto contains a signal for that target localization, e.g., a nuclear localization signal.
  • the soft tissue sarcoma cancer antibodies of the invention specifically bind to soft tissue sarcoma cancer proteins.
  • specifically bind herein is meant that the antibodies bind to the protein with a K ⁇ j of at least about 0.1 mM, more usually at least about 1 ⁇ M, preferably at least about 0.1 ⁇ M or better, and most preferably, 0.01 ⁇ M or better. Selectivity of binding to the specific target and not to related sequences is often also important
  • the RNA expression levels of genes are determined for different cellular states in the soft tissue sarcoma cancer phenotype. Expression levels of genes in normal tissue (e.g., not exhibiting soft tissue sarcoma cancer) and in soft tissue sarcoma cancer tissue (and in some cases, for varying severities of soft tissue sarcoma cancer that relate to prognosis, as outlined below) are evaluated to provide expression profiles.
  • An expression profile of a particular cell state or point of development is essentially a "finge ⁇ rint" of the state. While two states may have a particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is reflective of the state of the cell.
  • differential expression refers to qualitative or quantitative differences in the temporal and/or cellular gene expression patterns within and among cells and tissue.
  • a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, e.g., normal versus cancer tissue.
  • Genes may be turned on or turned off in a particular state, relative to another state thus permitting comparison of two or more states.
  • a qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques. Some genes will be expressed in one state or cell type, but not in both.
  • the difference in expression may be quantitative, e.g., in that expression is increased or decreased; e.g., gene expression is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript.
  • the degree to which expression differs need only be large enough to quantify via standard characterization techniques, e.g., as by use of Affymetrix GENECHIP ® expression anays. See, Lockhart (1996) Nature Biotechnology 14:1675-1680.
  • Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, Northern analysis and RNase protection.
  • the change in expression is at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably at least about 200%, with from 300 to at least 1000% being especially useful.
  • Evaluation may be at the gene transcript, or the protein level.
  • the amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, e.g., with antibodies to the soft tissue sarcoma cancer protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc.
  • Proteins conesponding to soft tissue sarcoma cancer genes e.g., those identified as being important in a soft tissue sarcoma cancer phenotype, can be evaluated in a soft tissue sarcoma cancer diagnostic test.
  • gene expression monitoring is performed simultaneously on a number of genes. Multiple protein expression monitoring can be performed as well. Similarly, these assays may be performed on an individual basis as well.
  • the soft tissue sarcoma cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of soft tissue sarcoma cancer sequences in a particular cell.
  • the assays are further described below in the example. PCR techniques can be used to provide greater sensitivity.
  • nucleic acids encoding the soft tissue sarcoma cancer protein are detected.
  • DNA or RNA encoding the soft tissue sarcoma cancer protein may be detected, of particular interest are methods wherein an mRNA encoding a cancer protein is detected.
  • Probes to detect mRNA can be a nucleotide/deoxynucleotide probe that is complementary to and hybridizes with the mRNA and includes, but is not limited to, oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein.
  • the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample. Following washing to remove the non-specifically bound probe, the label is detected. In another method detection of the mRNA is performed in situ.
  • permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA.
  • a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA.
  • the label is detected.
  • a digoxygenin labeled riboprobe that is complementary to the mRNA encoding a cancer protein is detected by binding the digoxygenin with an anti- digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5- bromo-4-chloro-3-indoyl phosphate.
  • various proteins from the three classes of proteins as described herein are used in diagnostic assays.
  • the soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing cancer sequences are used in diagnostic assays. This can be performed on an individual gene or conesponding polypeptide level.
  • the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes and/or conesponding polypeptides.
  • soft tissue sarcoma cancer proteins find use as markers of soft tissue sarcoma cancer, e.g., for prognostic or diagnostic pu ⁇ oses. Detection of these proteins in putative soft tissue sarcoma cancer tissue allows for detection, prognosis, or diagnosis of cancer, and for selection of therapeutic strategy.
  • antibodies are used to detect soft tissue sarcoma cancer proteins.
  • One method separates proteins from a sample by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be another type of gel, including isoelectric focusing gels and the like).
  • the cancer protein is detected, e.g., by immunoblotting with antibodies raised against the cancer protein.
  • antibodies to the soft tissue sarcoma cancer protein find use in in situ imaging techniques, e.g., in histology. See, e.g., Asai, et al. (eds. 1993) Methods in Cell Biology: Antibodies in Cell Biology (vol. 37) Academic Press.
  • cells are contacted with from one to many antibodies to the soft tissue sarcoma cancer protein(s). Following washing to remove non-specific antibody binding, the presence of the antibody or antibodies is detected.
  • the antibody is detected by incubating with a secondary antibody that contains a detectable label.
  • the primary antibody to the soft tissue sarcoma cancer protein(s) contains a detectable label, e.g., an enzyme marker that can act on a substrate.
  • each one of multiple primary antibodies contains a distinct and detectable label.
  • This method finds particular use in simultaneous screening for a plurality of soft tissue sarcoma cancer proteins. Many other histological imaging techniques are also provided by the invention.
  • the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths.
  • a fluorescence activated cell sorter FACS
  • FACS fluorescence activated cell sorter
  • antibodies find use in diagnosing soft tissue sarcoma cancer from biological samples, such as blood, urine, sputum, semen, or other bodily fluids.
  • biological samples such as blood, urine, sputum, semen, or other bodily fluids.
  • certain cancer proteins are secreted/circulating molecules. Blood or semen samples, therefore, are useful as samples to be probed or tested for the presence of secreted cancer proteins.
  • Antibodies can be used to detect a soft tissue sarcoma cancer protein by previously described immunoassay techniques including ELISA, immunoblotting (Western blotting), immunoprecipitation, BIACORE technology and the like. Conversely, the presence of antibodies may indicate an immune response against an endogenous soft tissue sarcoma cancer protein.
  • in situ hybridization of labeled cancer nucleic acid probes to tissue anays is done. For example, anays of tissue samples, including cancer tissue and/or normal tissue, are made. In situ hybridization (see, e.g., Ausubel, supra) is then performed. When comparing the finge ⁇ rints between an individual and a standard, the skilled artisan can make a diagnosis, a prognosis, or a prediction based on the findings. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis and molecular profiling of the condition of the cells may lead to distinctions between responsive or refractory conditions or may be predictive of outcomes.
  • the cancer proteins, antibodies, nucleic acids, modified proteins and cells containing cancer sequences are used in prognosis assays.
  • gene expression profiles can be generated that conelate to soft tissue sarcoma cancer severity, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes included.
  • P-glycoprotein and Ki-67 antigen are promising markers for 5-year overall and disease-free survival for soft tissue sarcoma patients.
  • Levine E.A. et al. Evaluation of new prognostic markers for adult soft tissue sarcomas, J. Clin. Oncol. 15:3249-57 (1997).
  • Other markers may be similarly identified that conelate to soft tissue sarcoma cancer severity, or survival rates of soft tissue sarcoma patients.
  • cancer probes may be attached to biochips for the detection and quantification of cancer sequences in a tissue or patient.
  • the assays proceed as outlined above for diagnosis.
  • PCR method may provide more sensitive and accurate quantification.
  • Genes useful in prognostic assays are genes that are differentially expressed according to the stage of illness of the patient.
  • the genes may be uniquely expressed according to the stage of the patient, h another embodiment, the genes may be expressed at differential levels according to the stage of the patient.
  • genes expressed in the different stages may be used to determine the viability of inducing remission in a patient.
  • genes that are expressed indicating onset of long-term complications may also be useful as a prognostic tool. Assays for therapeutic compounds
  • the soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing soft tissue sarcoma cancer sequences are used in drag screening assays or by evaluating the effect of drag candidates on a "gene expression profile" or expression profile of polypeptides.
  • the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow momtoring for expression profile genes after treatment with a candidate agent. See, e.g., Zlokarnik, et al. (1998) Science 279:84-88; and Heid (1996) Genome Res. 6:986-994.
  • the soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified soft tissue sarcoma cancer proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the soft tissue sarcoma cancer phenotype or an identified physiological function of a soft tissue sarcoma cancer protein. As above, this can be done on an individual gene level or by evaluating the effect of drag candidates on a "gene expression profile". In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow momtoring for expression profile genes after treatment with a candidate agent, see Zlokamik, supra.
  • assays may be executed.
  • assays may be run on an individual gene or protein level. That is, having identified a particular gene as up regulated in soft tissue sarcoma cancer, test compounds can be screened for the ability to modulate gene expression or for binding to the cancer protein.
  • “Modulation” thus includes both an increase and a decrease in gene expression. The amount of modulation will depend on the original change of the gene expression in normal versus tissue exhibiting soft tissue sarcoma cancer, with changes of at least about 10%), preferably about 50%, more preferably about 100-300%, and in some embodiments 300-1000% or greater.
  • a gene exhibits a 4-fold increase in cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in cancer tissue compared to no ⁇ nal tissue often provides a target value of a 10-fold increase in expression to be induced by the test compound.
  • the amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, e.g., through the use of antibodies to the cancer protein and standard immunoassays. Proteomics and separation techniques may also allow quantification of expression.
  • gene expression or protein monitoring of a number of entities is monitored simultaneously.
  • Such profiles will typically involve a plurality of those entities described herein.
  • the soft tissue sarcoma cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of cancer sequences in a particular cell.
  • PCR may be used.
  • a series e.g., of microtiter plate, may be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.
  • Expression monitoring can be performed to identify compounds that modify the expression of one or more soft tissue sarcoma cancer-associated sequences, e.g., a polynucleotide sequence set out in the Tables.
  • a test modulator is added to the cells prior to analysis.
  • screens are also provided to identify agents that modulate soft tissue sarcoma cancer, modulate soft tissue sarcoma cancer proteins, bind to a soft tissue sarcoma cancer protein, or interfere with the binding of a soft tissue sarcoma cancer protein and an antibody or other binding partner:
  • test compound or “drag candidate” or “modulator” or grammatical equivalents as used herein describes a molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the cancer phenotype or the expression of a cancer sequence, e.g., a nucleic acid or protein sequence, h several embodiments, modulators alter expression profiles, or expression profile nucleic acids or proteins provided herein.
  • the modulator suppresses a soft tissue sarcoma cancer phenotype, e.g., to a normal tissue finge ⁇ rint.
  • a modulator induced a cancer phenotype In another embodiment, a modulator induced a cancer phenotype.
  • a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations.
  • one of these concentrations serves as a negative control, e.g., at zero concentration or below the level of detection.
  • Dmg candidates encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 daltons. Small molecules may be less than 2000, or less than 1500, or less than 1000, or less than 500 D.
  • Candidate agents comprise functional groups necessary for stractural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups.
  • the candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups.
  • Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, stractural analogs, or combinations thereof. Particularly useful are peptides.
  • a modulator will neutralize the effect of a soft tissue sarcoma cancer protein.
  • neutralize is meant that activity of a protein is inhibited or blocked and thereby has substantially no effect on a cell.
  • combinatorial libraries of potential modulators will be screened for an ability to bind to a soft tissue sarcoma cancer polypeptide or to modulate activity.
  • new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound") with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds.
  • high throughput screening (HTS) methods are employed for such an analysis. See, e.g., Janzen (2002) High Throughput Screening: Methods and Protocols Humana; Devlin (ed. 1997) High Throughput Screening: The Discovery of Bioactive Substances Dekker; and Mei and Czamik (eds. 2002) Integrated Drag Discovery Techniques Dekker.
  • high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such "combinatorial chemical libraries" are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds” or can themselves be used as potential or actual therapeutics.
  • a combinatorial chemical library is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks” such as reagents.
  • a linear combinatorial chemical library such as a polypeptide (e.g., mutein) library
  • a polypeptide e.g., mutein
  • Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks. See Gallop, et al. (1994) J. Med. Chem. 37:1233-1251. Preparation and screening of combinatorial chemical libraries is well known.
  • Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., US Patent No. 5,010,175, Furka (1991) Pept. Prot. Res. 37:487-493, Houghton, et al. (1991) Nature 354:84-88), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091), benzodiazepines (US Pat. No. 5,288,514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs, et al.
  • peptide libraries see, e.g., US Patent No. 5,010,175, Furka (1991) Pept. Prot. Res. 37:487-493, Houghton, et al. (1991) Nature 354:84-88
  • a number of well known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations like the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Co ⁇ oration, Hopkinton, MA; Orca, Hewlett-Packard, Palo Alto, CA), which mimic the manual synthetic operations performed by a chemist.
  • the above devices are suitable for use with the present invention. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent.
  • numerous combinatorial libraries are themselves commercially available.
  • Assays thus detect enhancement or inhibition of cancer gene transcription, inhibition or enhancement of polypeptide expression, and inhibition or enhancement of polypeptide activity.
  • High throughput assays for the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known, as are binding assays and reporter gene assays.
  • US Patent No. 5,559,410 discloses high throughput screening methods for proteins
  • US Patent No. 5,585,639 discloses high throughput screening methods for nucleic acid binding (e.g., in anays)
  • US Patent Nos. 5,576,220 and 5,541,061 disclose high throughput methods of screening for ligand/antibody binding.
  • high throughput screening systems are commercially available. See, e.g., Zymark Co ⁇ ., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc., Fullerton, CA; Precision Systems, Inc., Natick, MA, etc. These systems typically automate entire procedures, including sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e.g., Zymark Co ⁇ . provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.
  • modulators are proteins, often naturally occurring proteins or fragments of naturally occurring proteins.
  • cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts may be used.
  • libraries of proteins may be made for screening in the methods of the invention.
  • Particularly useful in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, including human proteins.
  • Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes or ligands and receptors.
  • modulators are peptides of from about 5-30 amino acids, with from about 5-20 amino acids being prefened, and from about 7-15 being particularly prefened.
  • the peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased” random peptides.
  • randomized or grammatical equivalents herein is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. Since generally these random peptides (or nucleic acids, discussed below) are chemically synthesized, they may inco ⁇ orate nucleotide or amino acid variations.
  • the synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.
  • the library is fully randomized, with no sequence preferences or constants.
  • the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities.
  • the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines, or histidines for phosphorylation sites, etc., or to purines, etc.
  • Modulators of soft tissue sarcoma cancer can also be nucleic acids, as defined above.
  • nucleic acid modulating agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids.
  • digests of prokaryotic or eukaryotic genomes maybe used as is outlined above for proteins.
  • the candidate compounds are organic chemical moieties, a wide variety of which are available in the literature. After the candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing a target sequence to be analyzed is added to the biochip. If required, the target sequence is prepared using known techniques.
  • the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate.
  • an in vitro transcription with labels covalently attached to the nucleotides is performed.
  • the nucleic acids are labeled with biotin- FITC or PE, or with cy3 or cy5.
  • the target sequence is labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe.
  • the label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected.
  • the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme.
  • the label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin.
  • the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.
  • These assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes. See, e.g., US Patent Nos. 5,681,702; 5,597,909; 5,545,730; 5,594,117; 5,591,584; 5,571,670; 5,580,731; 5,571,670; 5,591,584; 5,624,802; 5,635,352; 5,594,118; 5,359,100; 5,124,246; and 5,681,697.
  • the target nucleic acid may be prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
  • hybridization conditions may be used in the present invention, including high, moderate, and low stringency conditions as outlined above.
  • the assays are generally run under stringency conditions which allows formation of the label probe hybridization complex only in the presence of target.
  • Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration, pH, organic solvent concentration, etc.
  • the reactions outlined herein may be accomplished in a variety of ways. Components of the reaction may be added simultaneously, or sequentially, in different orders, with several embodiments outlined below.
  • the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g., albumin, detergents, etc., which may be used to facilitate optimal hybridization and detection, and/or reduce non-specific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target.
  • the assay data are analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.
  • Screens are performed to identify modulators of the soft tissue sarcoma cancer phenotype.
  • screening is performed to identify modulators that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype.
  • screens can be performed to identify modulators that alter expression of individual genes.
  • screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product.
  • screens can be done for genes that are induced in response to a candidate agent.
  • a screen as described above can be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated soft tissue sarcoma cancer tissue reveals genes that are not expressed in normal tissue or soft tissue sarcoma cancer tissue, but are expressed in agent treated tissue.
  • agent-specific sequences can be identified and used by methods described herein for cancer genes or proteins. In particular, these sequences and the proteins they encode find use in marking or identifying agent treated cells.
  • a test compound is administered to a population of cancer cells, that have an associated soft tissue sarcoma cancer expression profile.
  • administration or “contacting” herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface.
  • nucleic acid encoding a proteinaceous candidate agent may be put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is achieved.
  • a viral construct such as an adenoviral or retroviral construct
  • Regulatable gene therapy systems can also be used.
  • the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
  • soft tissue sarcoma cancer tissue may be screened for agents that modulate, e.g., induce or suppress the cancer phenotype.
  • a change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on the cancer activity.
  • screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself can be done.
  • the gene products of differentially expressed genes are sometimes refened to herein as “cancer proteins” or a “cancer modulatory protein”.
  • the cancer modulatory protein may be a fragment, or alternatively, be the full length protein to the fragment encoded by the nucleic acids of the Tables.
  • the cancer modulatory protein is a fragment.
  • the cancer amino acid sequence which is used to determine sequence identity or similarity is encoded by a nucleic acid of the Tables, hi another embodiment, the sequences are naturally occurring allelic variants of a protein encoded by a nucleic acid of the Tables. In another embodiment, the sequences are sequence variants as further described herein.
  • the cancer modulatory protein is a fragment of approximately 14-
  • the fragment is a soluble fragment.
  • the fragment includes a non-transmembrane region.
  • the fragment has an N-terminal Cys to aid in solubility.
  • the C-terminus of the fragment is kept as a free acid and the N-terminus is a free amine to aid in coupling, e.g., to cysteine.
  • cancer proteins are conjugated to an immunogenic agent as discussed herein, h one embodiment the cancer protein is conjugated to BSA
  • Measurements of soft tissue sarcoma cancer polypeptide activity, or of soft tissue sarcoma cancer or cancer phenotype can be performed using a variety of assays.
  • the effects of the test compounds upon the function of the soft tissue sarcoma cancer polypeptides can be measured by examining parameters described above.
  • a suitable physiological change that affects activity can be used to assess the influence of a test compound on the polypeptides of this invention.
  • mammalian soft tissue sarcoma cancer polypeptide is typically used, e.g., mouse, preferably human.
  • Assays to identify compounds with modulating activity can be performed in vitro.
  • a soft tissue sarcoma cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from about 0.5- 48 hours.
  • the soft tissue sarcoma cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA.
  • the level of protein is typically measured using immunoassays such as western blotting, ELISA, and the like with an antibody that selectively binds to the soft tissue sarcoma cancer polypeptide or a fragment thereof.
  • amplification e.g., using PCR, LCR, or hybridization assays, e.g., northern hybridization, RNAse protection, dot blotting
  • hybridization assays e.g., northern hybridization, RNAse protection, dot blotting
  • the level of protein or mRNA is typically detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.
  • a reporter gene system can be devised using a soft tissue sarcoma cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or ⁇ -gal.
  • the reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques.
  • screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself can be done.
  • the gene products of differentially expressed genes are sometimes refened to herein as "soft tissue sarcoma cancer proteins.”
  • the soft tissue sarcoma cancer protein may be a fragment, or alternatively, the full length protein to a fragment shown herein.
  • screening for modulators of expression of specific genes is performed. Typically, the expression of only one or a few genes are evaluated.
  • screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity.
  • variants can be further screened to better evaluate stracture activity relationships.
  • binding assays are done.
  • purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made.
  • antibodies are generated to the protein gene products, and standard immunoassays are run to determine the amount of protein present.
  • cells comprising the soft tissue sarcoma cancer proteins can be used in the assays.
  • the methods comprise combining a soft tissue sarcoma cancer protein and a candidate compound, and determining the binding of the compound to the soft tissue sarcoma cancer protein.
  • Other embodiments utilize the human soft tissue sarcoma cancer protein, although other mammalian proteins may also be used, e.g., for the development of animal models of human disease.
  • variant or derivative soft tissue sarcoma cancer proteins may be used.
  • the soft tissue sarcoma cancer protein or the candidate agent is non-diffusibly bound to an insoluble support, preferably having isolated sample receiving areas (e.g., a microtiter plate, an array, etc.).
  • the insoluble supports may be made of a composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening.
  • the surface of such supports may be solid or porous and of a convenient shape.
  • suitable insoluble supports include microtiter plates, anays, membranes and beads. These are typically made of glass, plastic (e.g., polystyrene), polysaccharides, nylon, or nitrocellulose, TEFLON ® (synthetic resinous flurorine-containing polymers), etc.
  • Microtiter plates and anays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples.
  • the particular manner of binding of the composition is typically compatible with the reagents and overall methods of the invention, maintains the activity of the composition, and is nondiffusable.
  • Other methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protein is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine semm albumin (BSA), casein, or other innocuous protein or other moiety.
  • BSA bovine semm albumin
  • the soft tissue sarcoma cancer protein is bound to the support, and a test compound is added to the assay.
  • the candidate agent is bound to the support and the cancer protein is added.
  • Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.), and the like.
  • the determination of the binding of the test modulating compound to the cancer protein may be done in many ways, hi one embodiment, the compound is labeled, and binding determined directly, e.g., by attaching all or a portion of the cancer protein to a solid support, adding a labeled candidate agent (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support.
  • a labeled candidate agent e.g., a fluorescent label
  • washing off excess reagent e.g., a fluorescent label
  • Various blocking and washing steps may be utilized as appropriate.
  • only one of the components is labeled, e.g., the proteins (or proteinaceous candidate compounds) can be labeled.
  • more than one component can be labeled with different labels, e.g., 125 I for the proteins and a fluorophor for the compound.
  • Proximity reagents e.g., quenching or energy transfer reagents are also useful.
  • the binding of the test compound is determined by competitive binding assay.
  • the competitor may be a binding moiety known to bind to the target molecule (e.g., a soft tissue sarcoma cancer protein), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding between the compound and the binding moiety, with the binding moiety displacing the compound.
  • the test compound is labeled. Either the compound, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at a temperature which facilitates optimal activity, typically between about 4-40° C. Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening. Typically between about 0.1-1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
  • the target molecule e.g., a soft
  • the competitor is added first, followed by a test compound.
  • Displacement of the competitor is an indication that the test compound is binding to the cancer protein and thus is capable of binding to, and potentially modulating, the activity of the cancer protein.
  • either component can be labeled.
  • the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate that the test compound is bound to the cancer protein with a higher affinity.
  • the presence of the label on the support, coupled with a lack of competitor binding may indicate that the test compound is capable of binding to the cancer protein.
  • the methods comprise differential screening to identity agents that are capable of modulating the activity of the cancer proteins
  • the methods comprise combining a cancer protein and a competitor in a first sample.
  • a second sample comprises a test compound, a cancer protein, and a competitor.
  • the binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the cancer protein.
  • differential screening is used to identify drag candidates that bind to the native soft tissue sarcoma cancer protein, but cannot bind to modified soft tissue sarcoma cancer proteins.
  • the stracture of the cancer protein may be modeled, and used in rational dmg design to synthesize agents that interact with that site. Drag candidates that affect the activity of the cancer protein are also identified by screening drags for the ability to either enhance or reduce the activity of the protein.
  • Positive controls and negative controls may be used in the assays.
  • control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, samples are washed free of non- specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
  • reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g., albumin, detergents, etc., which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in an order that provides for the requisite binding.
  • the invention provides methods for screening for a compound capable of modulating the activity of a cancer protein.
  • the methods comprise adding a test compound, as defined above, to a cell comprising cancer proteins.
  • Useful cell types include almost any cell.
  • the cells contain a recombinant nucleic acid that encodes a cancer protein.
  • a library of candidate agents are tested on a plurality of cells.
  • the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (e.g., cell-cell contacts).
  • physiological signals e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (e.g., cell-cell contacts).
  • the determinations are determined at different stages of the cell cycle process.
  • a method of inhibiting soft tissue sarcoma cancer cell division comprises administration of a soft tissue sarcoma cancer inhibitor.
  • a method of inhibiting soft tissue sarcoma cancer is provided.
  • the method may comprise administration of a soft tissue sarcoma cancer inhibitor, hi a further embodiment, methods of treating cells or individuals with soft tissue sarcoma cancer are provided, e.g., comprising administration of a soft tissue sarcoma cancer inhibitor.
  • a soft tissue sarcoma cancer inhibitor is an antibody as discussed above. In another embodiment, the soft tissue sarcoma cancer inhibitor is an antisense molecule.
  • Normal cells require a solid substrate to attach and grow. When the cells are transformed, they lose this phenotype and grow detached from the substrate.
  • transformed cells can grow in stined suspension culture or suspended in semi-solid media, such as semi-solid or soft agar.
  • the transformed cells when transfected with tumor suppressor genes, regenerate normal phenotype and require a solid substrate to attach and grow.
  • Soft agar growth or colony formation in suspension assays can be used to identify modulators of soft tissue sarcoma cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation.
  • a therapeutic compound would reduce or eliminate the host cells' ability to grow in stined suspension culture or suspended in semi-solid media, such as semi-solid or soft.
  • labeling index with (3H)-thymidine at saturation density can be used to measure density limitation of growth. See Freshney (2000), supra.
  • the transformed cells when transfected with tumor suppressor genes, regenerate a normal phenotype and become contact inhibited and would grow to a lower density.
  • labeling index with (3H)-thymidine at saturation density is a method of measuring density limitation of growth.
  • Transformed host cells are transfected with a soft tissue sarcoma cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions.
  • the percentage of cells labeling with (3H)-thymidine is determined autoradiographically. See, Freshney (1998), supra.
  • Transformed cells typically have a lower serum dependence than their normal counte ⁇ arts. See, e.g., Temin (1966) J. Nat'l Cancer Inst. 37:167-175; Eagle, et al. (1970) J. Exp. Med. 131:836-879; Freshney, supra. This is in part due to release of various growth factors by the transformed cells. Growth factor or serum dependence of transformed host cells can be compared with that of control.
  • Tumor cells release an increased amount of certain factors (hereinafter "tumor specific markers”) than their normal counte ⁇ arts.
  • tumor specific markers For example, plasminogen activator (PA) is released from human glioma at a higher level than from normal brain cells. See, e.g., Gullino "Angiogenesis, tumor vascularization, and potential interference with tumor growth” pp. 178-184 in Mihich (ed. 1985) Biological Responses in Cancer Plenum.
  • tumor angiogenesis factor TAF is released at a higher level in tumor cells than their normal counte ⁇ arts. See, e.g., Folkman (1992) "Angiogenesis and Cancer” Sem Cancer Biol. 3:89-96.
  • the degree of invasiveness into Matrigel or some other extracellular matrix constituent can be used as an assay to identify compounds that modulate soft tissue sarcoma cancer-associated sequences.
  • Tumor cells exhibit a good conelation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent.
  • tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells.
  • the level of invasion of host cells can be measured by using filters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 125 I and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra.
  • Knock-out transgenic mice can be made, in which the cancer gene is dismpted or in which a cancer gene is inserted.
  • Knock-out transgenic mice can be made by insertion of a marker gene or other heterologous gene into the endogenous cancer gene site in the mouse genome via homologous recombination.
  • Such mice can also be made by substituting the endogenous cancer gene with a mutated version of the cancer gene, or by mutating the endogenous cancer gene, e.g., by exposure to carcinogens.
  • a DNA construct is introduced into the nuclei of embryonic stem cells.
  • mice containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re-implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells partially derived from the mutant cell line. Therefore, by breeding the chimeric mice it is possible to obtain a new line of mice containing the introduced genetic lesion. See, e.g., Capecchi, et al. (1989) Science 244:1288-1292. Chimeric targeted mice can be derived according to Hogan, et al. (1988) Manipulating the Mouse Embryo: A Laboratory Manual CSH Press; and Robertson (ed.
  • Transplantable tumor cells (typically about 10° " cells) injected into iso genie hosts will produce invasive tumors in a high proportions of cases, while normal cells of similar origin will not.
  • cells expressing a soft tissue sarcoma cancer-associated sequences are injected subcutaneously.
  • tumor growth is measured (e.g., by volume or by its two largest dimensions) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth.
  • the activity of a soft tissue sarcoma cancer-associated protein is downregulated, or entirely inhibited, by the use of antisense polynucleotide, e.g., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a soft tissue sarcoma cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA.
  • antisense polynucleotide e.g., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a soft tissue sarcoma cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of
  • antisense polynucleotides can comprise naturally-occurring nucleotides, or synthetic species formed from naturally-occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter-sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species. Analogs are comprehended by this invention so long as they function effectively to hybridize with the soft tissue sarcoma cancer protein mRNA. See, e.g., Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA.
  • antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems. The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known.
  • Antisense molecules as used herein include antisense or sense oligonucleotides. Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti-sense strand.
  • the antisense and sense oligonucleotide comprise a single-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for soft tissue sarcoma cancer molecules.
  • An antisense molecule is for a soft tissue sarcoma cancer sequence in Tables 1 A-l IC, or for a ligand or activator thereof.
  • Antisense or sense oligonucleotides, according to the present invention comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides.
  • RNA interference is a mechanism to suppress gene expression in a sequence specific manner. See, e.g., Bru elkamp, et al. (2002) Sciencexpress (21March2002); Sha ⁇ (1999) Genes Dev. 13:139-141; and Cathew (2001) Cun. Op. Cell Biol. 13:244-248.
  • siRNA double stranded small interfering RNAs
  • the mechanism may be used to downregulate expression levels of identified genes, e.g., treatment of or validation of relevance to disease.
  • Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of soft tissue sarcoma cancer-associated nucleotide sequences.
  • a ribozyme is an RNA molecule that catalytically cleaves other RNA molecules.
  • ribozymes Different kinds have been described, including group I ribozymes, hammerhead ribozymes, hai ⁇ in ribozymes, RNase P, and axhead ribozymes. See, e.g., Castanotto, et al. (1994) Adv. in Pharmacology 25:289-317.
  • hai ⁇ in ribozymes General features of hai ⁇ in ribozymes are described, e.g., in Hampel, et al.
  • Patent No. 5,254,678 Methods of preparation are available. See, e.g., WO 94/26877;
  • Polynucleotide modulators of soft tissue sarcoma cancer may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753.
  • Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors.
  • conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its conesponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell.
  • a polynucleotide modulator of soft tissue sarcoma cancer may be introduced into a cell containing the target nucleic acid sequence, e.g., by formation of an polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.
  • methods of modulating soft tissue sarcoma cancer in cells or organisms comprise administering to a cell an anti-soft tissue sarcoma cancer antibody that reduces or eliminates the biological activity of an endogenous soft tissue sarcoma cancer protein.
  • the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a soft tissue sarcoma cancer protein. This may be accomplished in many ways. In one embodiment, e.g., when the soft tissue sarcoma cancer sequence is down-regulated in soft tissue sarcoma cancer, such state may be reversed by increasing the amount of soft tissue sarcoma cancer gene product in the cell.
  • the gene therapy techniques include the inco ⁇ oration of the exogenous gene using enhanced homologous recombination (EHR), e.g., as described in PCT/US93/03868, hereby inco ⁇ orated by reference in its entirety.
  • EHR enhanced homologous recombination
  • the activity of the endogenous soft tissue sarcoma cancer gene is decreased, e.g., by the administration of a soft tissue sarcoma cancer antisense nucleic acid or other inhibitor, such as RNAi.
  • the soft tissue sarcoma cancer proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to soft tissue sarcoma cancer proteins.
  • the soft tissue sarcoma cancer proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify cancer antibodies useful for production, diagnostic, or therapeutic purposes.
  • the antibodies are generated to epitopes unique to a cancer protein; that is, the antibodies show little or no cross- reactivity to other proteins.
  • the soft tissue sarcoma cancer antibodies may be coupled to standard affinity chromatography columns and used to purify cancer proteins.
  • the antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the cancer protein.
  • the invention provides methods for identifying cells containing variant soft tissue sarcoma cancer genes, e.g., determining all or part of the sequence of at least one endogenous soft tissue sarcoma cancer gene in a cell. This may be accomplished using known sequencing techniques.
  • the invention provides methods of identifying the cancer genotype of an individual, e.g., determining all or part of the sequence of at least one soft tissue sarcoma cancer gene of the individual.
  • the method may include comparing the sequence of the sequenced soft tissue sarcoma cancer gene to a known soft tissue sarcoma cancer gene, e.g., a wild-type gene.
  • the sequence of all or part of the soft tissue sarcoma cancer gene can then be compared to the sequence of a known soft tissue sarcoma cancer gene to determine if differences exist. This can be done using known homology programs, such as Bestfit, etc.
  • the presence of a difference in the sequence between the soft tissue sarcoma cancer gene of the patient and the known soft tissue sarcoma cancer gene conelates with a disease state or a propensity for a disease state, as outlined herein.
  • the soft tissue sarcoma cancer genes are used as probes to determine the number of copies of the soft tissue sarcoma cancer gene in the genome.
  • the soft tissue sarcoma cancer genes are used as probes to determine the chromosomal localization of the soft tissue sarcoma cancer genes.
  • Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the soft tissue sarcoma cancer gene locus.
  • a therapeutically effective dose of a soft tissue sarcoma cancer protein or modulator thereof is administered to a patient.
  • therapeutically effective dose herein is meant a dose that produces effects for which it is administered. The exact dose will depend on the pu ⁇ ose of the treatment, and can be ascertained using known techniques. See, e.g., Ansel, et al. (1999) Pharmaceutical Dosage Forms and Drag Delivery Lippincott; Lieberman (1992) Pharmaceutical Dosage Fomis (vols. 1-3) Dekker, ISBN 0824770846, 082476918X, 0824712692, 0824716981; Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding Amer.
  • a "patient” for the purposes of the present invention includes both humans and other animals, particularly mammals. Thus the methods are applicable to both human therapy and veterinary applications.
  • the patient is a mammal, preferably a primate, including humans.
  • the administration of the soft tissue sarcoma cancer proteins and modulators thereof of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, intranasally, transdermally topically, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly.
  • the soft tissue sarcoma cancer proteins and modulators may be directly applied as a solution, spray, or ointment.
  • the pharmaceutical compositions of the present invention comprise a soft tissue sarcoma cancer protein in a form suitable for administration to a patient.
  • the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts.
  • “Pharmaceutically acceptable acid addition salt” refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyravic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like.
  • “Pharmaceutically acceptable base addition salts” include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Particularly useful are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
  • the phannaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, com and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol.
  • carrier proteins such as serum albumin
  • buffers such as buffers
  • fillers such as microcrystalline cellulose, lactose, com and other starches
  • binding agents such as microcrystalline cellulose, lactose, com and other starches
  • binding agents such as microcrystalline cellulose, lactose, com and other starches
  • binding agents such as microcrystalline cellulose, lactose, com and other starches
  • sweeteners and other flavoring agents such as a cellulose, lactose, com and other starches
  • binding agents such as microcrystalline cellulose, lactose, com and other starches
  • sweeteners and other flavoring agents such as coloring agents
  • polyethylene glycol such as polyethylene glycol.
  • compositions for administration will commonly comprise a soft tissue sarcoma cancer protein modulator dissolved in a pharmaceutically acceptable carrier, preferably an aqueous carrier.
  • a pharmaceutically acceptable carrier preferably an aqueous carrier.
  • aqueous carriers can be used, e.g., buffered saline and the like. These solutions are sterile and generally free of undesirable matter.
  • These compositions may be sterilized by conventional, well known sterilization techniques.
  • the compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate, and the like.
  • the concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight, and the like in accordance with the particular mode of administration selected and the patient's needs. See, e.g., (1980) Remington's Pharmaceutical Science (18th ed.) Mack; and Hardman and Limbird (eds. 2001) Goodman and Gilman: The Pharmacological Basis of Therapeutics (10th ed.) McGraw-Hill.
  • a typical pharmaceutical composition for intravenous admimstration would be about 0.1 to 10 mg per patient per day. Dosages from about 0.1 to 100 mg per patient per day may be used, particularly when the drag is administered to a secluded site and not into the blood stream, such as into a body cavity or into a lumen of an organ. Substantially higher dosages are possible in topical administration. Actual methods for preparing parenterally administrable compositions will be known or apparent.
  • compositions containing modulators of soft tissue sarcoma cancer proteins can be administered for therapeutic or prophylactic treatments, h therapeutic applications, compositions are administered to a patient suffering from a disease (e.g., a cancer) in an amount sufficient to cure or at least partially anest the disease and its complications.
  • a disease e.g., a cancer
  • An amount adequate to accomplish this is defined as a "therapeutically effective dose.” Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health.
  • Single or multiple administrations of the compositions maybe administered depending on the dosage and frequency as required and tolerated by the patient.
  • the composition should provide a sufficient quantity of the agents of this invention to effectively treat the patient.
  • An amount of modulator that is capable of preventing or slowing the development of soft tissue sarcoma cancer in a mammal is refened to as a
  • prophylactically effective dose The particular dose required for a prophylactic treatment will depend upon the medical condition and history of the mammal, the particular stage or form of soft tissue sarcoma cancer disorder being prevented, as well as other factors such as age, weight, gender, administration route, efficiency, etc.
  • prophylactic treatments may be used, e.g., in a mammal who has previously had cancer to prevent a recurrence of the cancer, or in a mammal who is suspected of having a significant likelihood of developing cancer, based, at least in part, upon gene expression profiles.
  • Vaccine strategies may be used, in either a DNA vaccine form, or protein vaccine.
  • the present soft tissue sarcoma cancer protein- modulating compounds can be administered alone or in combination with additional soft tissue sarcoma cancer modulating compounds or with other therapeutic agent, e.g., other anti-cancer agents or treatments.
  • one or more nucleic acids e.g., polynucleotides comprising nucleic acid sequences set forth in Tables 1A-11C, such as RNAi, antisense polynucleotides, or ribozymes, will be introduced into cells, in vitro or in vivo.
  • the present invention provides methods, reagents, vectors, and cells useful for expression of soft tissue sarcoma cancer-associated polypeptides and nucleic acids using in vitro (cell-free), ex vivo, or in vivo (cell or organism-based) recombinant expression systems.
  • the particular procedure used to introduce the nucleic acids into a host cell for expression of a protein or nucleic acid is application specific. Many procedures for introducing foreign nucleotide sequences into host cells may be used. These include the use of calcium phosphate transfection, spheroplasts, electroporation, liposomes, microinjection, plasma vectors, viral vectors, and other well known methods for introducing cloned genomic DNA, cDNA, synthetic DNA, or other foreign genetic material into a host cell. See, e.g., Berger and Kimmel (1987) Guide to Molecular Cloning Techniques from Methods in Enzymology (vol. 152) Academic Press; Ausubel, et al. (eds. 1999 and supplements) Cunent Protocols Lippincott; and
  • soft tissue sarcoma cancer proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above.
  • cancer genes (including both the full-length sequence, partial sequences, or regulatory sequences of the cancer coding regions) can be administered in a gene therapy application. These cancer genes can include inhibitory applications, e.g., inhibitory RNA, gene therapy (e.g., for inco ⁇ oration into the genome), or antisense compositions.
  • Soft tissue sarcoma cancer polypeptides and polynucleotides can also be administered as vaccine compositions to stimulate HTL, CTL, and antibody responses.
  • Such vaccine compositions can include, e.g., lipidated peptides (see, e.g., Vitiello, et al. (1995) J. Clin. Invest. 95:341-349), peptide compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG") microspheres (see, e.g., Eldridge, et al. (1991) Molec. Immunol. 28:287-294; Alonso, et al. (1994) Vaccine 12:299-306; Jones, et al.
  • PLG poly(DL-lactide-co-glycolide)
  • Vaccine 13:675-681 peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e.g., Takahashi, et al. (1990) Nature 344:873- 875; Hu, et al. (1998) Clin. Exp. Immunol. 113:235-243), multiple antigen peptide systems (MAPs) (see, e.g., Tam (1988) Proc. Nat'l Acad. Sci. USA 85:5409-5413; Tam (1996) J. Immunol. Meth.
  • ISCOMS immune stimulating complexes
  • MAPs multiple antigen peptide systems
  • peptides formulated as multivalent peptides peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery vectors (Perkus, et al., p. 379, inKaufmann (ed. 1996) Concepts in Vaccine Development de Gruyter; Chakrabarti, et al. (1986) Nature 320:535-537; Hu, et al. (1986) Nature 320:537-540; Kieny, et al. (1986) Bio/Technology 4:790-795;
  • Toxin-targeted delivery technologies also known as receptor mediated targeting, such as those of Avant hnmunotherapeutics, Inc. (Needham, MA) may also be used.
  • Vaccine compositions often include adjuvants.
  • Many adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins.
  • adjuvants are commercially available as, e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A; and quil A.
  • Cytokines such as GM-CSF, interleukin-2, -7, -12, and other like growth factors, may also be used as adjuvants.
  • Vaccines can be administered as nucleic acid compositions wherein DNA or RNA encoding one or more of the polypeptides, or a fragment thereof, is administered to a patient. See, e.g., Wolff, et al. (1990) Science 247:1465-1468 as well as US Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720; and in more detail below.
  • DNA-based delivery technologies include "naked DNA”, facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated (“gene gun") or pressure-mediated delivery (see, e.g., US Patent No. 5,922,687).
  • the peptides of the invention can be expressed by viral or bacterial vectors.
  • expression vectors include attenuated viral hosts, such as vaccinia or fowlpox. This approach involves the use of vaccinia virus, e.g., as a vector to express nucleotide sequences that encode cancer polypeptides or polypeptide fragments.
  • vaccinia viras Upon introduction into a host, the recombinant vaccinia viras expresses the immunogenic peptide, and thereby elicits an immune response.
  • Vaccinia vectors and methods useful in immunization protocols are described, e.g., in US Patent No. 4,722,848.
  • Another vector is BCG (Bacille Calmette Guerin). See Stover, et al. (1991) Nature 351:456-460.
  • BCG Bacille Calmette Guerin
  • a wide variety of other vectors are available for therapeutic administration or immunization, e.g., adeno and adeno-associated virus vectors, refroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like.
  • Methods for the use of genes as DNA vaccines are well known, and include placing a cancer gene or portion of a cancer gene under the control of a regulatable promoter or a tissue-specific promoter for expression in a soft tissue sarcoma cancer patient.
  • the soft tissue sarcoma cancer gene used for DNA vaccines can encode full- length soft tissue sarcoma cancer proteins, but more preferably encodes portions of the cancer proteins including peptides derived from the cancer protein.
  • a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from a soft tissue sarcoma cancer gene.
  • soft tissue sarcoma cancer-associated genes or sequence encoding subfragments of a soft tissue sarcoma cancer protein are introduced into expression vectors and tested for their immunogenicity in the context of Class I MHC and an ability to generate cytotoxic T cell responses. This procedure provides for production of cytotoxic T cell responses against cells which present antigen, including intracellular epitopes.
  • the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine.
  • adjuvant molecules include cytokines that increase the immunogenic response to the soft tissue sarcoma cancer polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are available.
  • soft tissue sarcoma cancer genes find use in generating animal models of soft tissue sarcoma cancer.
  • gene therapy technology e.g., wherein antisense RNA directed to the soft tissue sarcoma cancer gene will also diminish or repress expression of the gene.
  • Animal models of soft tissue sarcoma cancer find use in screening for modulators of a soft tissue sarcoma cancer-associated sequence or modulators of soft tissue sarcoma cancer.
  • transgenic animal technology including gene knockout technology, e.g., as a result of homologous recombination with an appropriate gene targeting vector, will result in the absence or increased expression of the soft tissue sarcoma cancer protein.
  • tissue-specific expression or knockout of the soft tissue sarcoma cancer protein may be necessary.
  • the soft tissue sarcoma cancer protein is overexpressed in soft tissue sarcoma cancer.
  • transgenic animals can be generated that overexpress the soft tissue sarcoma cancer protein.
  • promoters of various strengths can be employed to express the transgene.
  • the number of copies of the integrated transgene can be determined and compared for a detennination of the expression level of the transgene. Animals generated by such methods find use as animal models of soft tissue sarcoma cancer and are additionally useful in screening for modulators to treat soft tissue sarcoma cancer or to evaluate a therapeutic entity. Kits for Use in Diagnostic and/or Prognostic Applications
  • kits are also provided by the invention, h the diagnostic and research applications such kits may include at least one of the following: assay reagents, buffers, soft tissue sarcoma cancer-specific nucleic acids or antibodies, hybridization probes and or primers, antisense polynucleotides, ribozymes, dominant negative soft tissue sarcoma cancer polypeptides or polynucleotides, small molecules inhibitors of cancer- associated sequences, etc.
  • a therapeutic product may include sterile saline or another pharmaceutically acceptable emulsion and suspension base.
  • the kits may include instructional materials containing directions
  • instructional materials typically comprise written or printed materials they are not limited to such.
  • a medium capable of storing such instructions and communicating them to an end user is contemplated by this invention.
  • Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like.
  • Such media may include addresses to internet sites that provide such instructional materials.
  • kits for screening for modulators of soft tissue sarcoma cancer-associated sequences can be prepared from readily available materials and reagents.
  • such kits can comprise one or more of the following materials: a soft tissue sarcoma cancer- associated polypeptide or polynucleotide, reaction tubes, and instructions for testing cancer-associated activity.
  • the kit contains biologically active soft tissue sarcoma cancer protein.
  • kits and components can be prepared according to the present invention, depending upon the intended user of the kit and the particular needs of the user. Diagnosis would typically involve evaluation of a plurality of genes or products. The genes will be selected based on conelations with important parameters in disease which may be identified in historical or outcome data.
  • Example 1 Tissue Preparation, Labeling Chips, and Fingerprints Purify total RNA from tissue using TRIZOL Reagent
  • tissue weight Homogenize tissue samples in 1ml of TRIZOL ® (chemical reagents for use in isolating biological material from organic tissue) per 50mg of tissue using a Polytron 3100 homogenizer.
  • the generator/probe used depends upon the tissue size. A generator that is too large for the amount of tissue to be homogenized will cause a loss of sample and lower RNA yield.
  • RNA PRECIPITATION Incubate samples at room temp, for 2-3 minutes. Centrifuge samples at 6500 ⁇ m in a Sorvall superspeed for 30 min. at 4°C. (You may spin at up to 12,000 x g for 10 min. but you risk breaking your tubes in the centrifuge.)
  • centrifuge for 2 minutes at 14,000 to 18,000 g. If centrifuge has a "soft setting,” then use it. Remove supernatant without disturbing Oligotex pellet. A little bit of solution can be left behind to reduce the loss of Oligotex. Save sup until certain that satisfactory binding and elution of poly A + mRNA has occuned. Gently resuspend in Wash Buffer OW2 and pipet onto spin column. Centrifuge the spin column at full speed (soft setting if possible) for 1 minute.
  • RNA Use 5ug of total RNA or lug of polyA+ mRNA as starting material.
  • For total RNA use 2ul of Superscript RT.
  • For polyA+ mRNA use lul of Superscript RT.
  • Final volume of first strand synthesis mix is 20ul.
  • RNA must be in a volume no greater than lOul.
  • Fragment RNA by incubation at 94 C for 35 minutes in 1 x Fragmentation buffer.
  • the labeled RNA transcript can be analyzed before and after fragmentation. Samples can be heated to 65C for 15 minutes and electrophoresed on 1% agarose/TBE gels to get an approximate idea of the transcript size range Hybridization 200 ul (lOug cRNA) of a hybridization mix is put on the chip. If multiple hybridizations are to be done (such as cycling through a 5 chip set), then it is recommended that an initial hybridization mix of 300 ul or more be made.
  • Hybrization Mix fragment labeled RNA (50ng/ul final cone.) 50 pM 948-b control oligo 1.5 pM BioB
  • RNA degradation 25mM of cold dATP, dCTP, and dGTP, lOmM of dTTP: 25 ⁇ l each of lOOmM dATP, dCTP, and dGTP; 10 ⁇ l of lOOmM dTTP to 15 ⁇ l H2O.
  • dNTPs from Pharmacia RNA degradation:
  • 0.2X SSC 5 min. 2.5 mis 20X SSC in 250mls H 2 O Dry slides in centrifuge, 1000 RPM, lmin.
  • Example 2 Gene Chip Analysis Molecular profiles of various normal and soft tissue sarcoma cancer tissues were determined and analyzed using gene chips. RNA was isolated and gene chip analysis was performed as described above (Glynne, et al. (2000) Nature 403:672- 676; Zhao, et al. (2000) Genes Dev. 14:981-993). The results are shown in the tables and figures that follow. These soft tissue sarcoma (STSD) associated sequences are identified in the tables by Genbank Accession numbers and gene titles. As indicated, some of the Accession numbers include expression sequence tags (ESTs). Thus, in one embodiment herein, genes within an expression profile, also termed expression profile genes, include ESTs and are not necessarily full length.
  • STSD soft tissue sarcoma
  • RATIO 95th percentile of chondrosarcomas AIs divided by the 50th percentile of normal tissue AIs , where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
  • cartilage oligomeric matrix protein (ps L32137 Hs.1584 29.0 1751 17526122
  • proteolipid protein 1 (Pelizaeus-Merzba N76497 Hs.355807 5.6 1086 5626
  • ADAMTS2 a disintegrin-like and metail AW378065 Hs.8687 5.5 4360 8190
  • proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs.355807 5.4 777 5386
  • RNA binding motif protein 8A AF198620 Hs.10283 4.3 4874885154

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Abstract

Described herein are methods and compositions that can be used for diagnosis and treatment of soft tissue sarcoma cancer phenotypes and soft tissue sarcoma cancer-associated diseases. Also described herein are methods that can be used to identify modulators of soft tissue sarcoma cancer.

Description

METHODS OF DETECTING SOFT TISSUE SARCOMA,
COMPOSITIONS AND METHODS OF SCREENING FOR SOFT
TISSUE SARCOMA MODULATORS
PRIORITY INFORMATION
This application claims the benefit of U.S. Provisional Application No. 60/429,739, filed November 26, 2002.
FIELD OF THE INVENTION The invention relates to the identification of nucleic acid and protein expression profiles and nucleic acids, products, and antibodies thereto that are involved in soft tissue sarcomas; and to the use of such expression profiles and compositions in diagnosis and therapy of such cancers. The invention further relates to methods for identifying and using agents and/or targets that modulate these cancers.
BACKGROUND OF THE INVENTION Background on Soft Tissue Sarcomas is available, e.g., from Montgomery and Aaron (2001) Clinical Pathology of Soft-Tissue Tumors Marcel Dekker; ISBN: 0824702905; Brennan, et al. "Soft tissue sarcoma" pp 1738-1788 in DeNita, et al. (eds. 1997) Cancer: Principles and Practice of Oncology (5th ed.) Lippincott-Raven Philadelphia, PA; Pisters, et al. (2001) Cancer Management: A Multidisciplinary Approach (5th ed.) PRR; p 127-137 in American Joint Committee on Cancer (1992) Manual for Staging of Cancer (4th ed.) Lippincott, . Philadelphia; Schajowicz (1994) Tumors and Tumor-like Lesions of Bone: Pathology, Radiology and Treatment (2d ed.) Springer- Verlag, NY; Cotran, et al. (1999) Pathologic Basis of Disease Saunders; and various websites, e.g., NCI, Memorial Sloan-Kettering Cancer Center; cancerindex.com; cancersource.com; cancernetwork.com; and sarcoma.net.
Soft-tissue sarcomas are rare, representing only about 1 percent of all cancer cases. According to the American Cancer Society, approximately 8,700 new cases of soft-tissue sarcoma are diagnosed each year in adults and children in the United States. The age-adjusted incidence is 2 cases per 100,000 persons. There is a slight male predominance, with a male to female ratio of 11 : 10. The age distribution in adult soft-tissue sarcoma studies is: <40 years, 20.7% of patients; 40-60 years, 27.6% of patients; > 60 years, 51.7% of patients.
In the United States, of the 8,700 new cases of soft-tissue sarcoma are identified annually, 4,400 patients die of the disease each year. The five-year survival percentages of soft tissue sarcomas range from 30% to 95% based on subtype and grade. The range for extremity sarcomas is 90%-95%, for trunk sarcomas 50%-75%, and for retroperitoneal lesions 30%-50%. In each of the three locations, higher-grade sarcomas have a poorer survival rate.
In a survey of approximately 5,000 soft-tissue sarcoma patients admitted to Memorial Sloan-Kettering Cancer Center from 1982 to 2001 : 32 percent of sarcomas were found in the lower extremities; 18 percent in the viscera (organs located within the chest and abdomen, such as the stomach, kidney, uterus, etc.); 15 percent in the abdominal and retroperitoneal region; 13 percent in the upper extremities; 8 percent in the trunk and 14 percent in other sites. The histological subtypes of soft tissue sarcomas include malignant fibrous histiocytoma, liposarcoma, fibrosarcoma, synovial sarcoma, rhabdomyosarcoma, and leiomyosarcoma. They occur over 50% of the time in extremities; the remainder occur in the head and neck and retroperitoneum. In addition, many of these tumors dedifferentiate. This results in a variety of overlapping patterns, making uniform classification difficult. The current histopathologic classification is based on the putative cell of origin of each lesion. Such classification based on histogenesis is reproducible for the more differentiated tumors. However, as the degree of histologic differentiation declines, it becomes increasingly difficult to determine cellular origin. Liposarcomas are malignant tumors that develop from fat tissue. They can develop anywhere in the body, but they most often grow in the retroperitoneum
(tissue at the back of the abdominal cavity). Fat tissue may also originate from other locations, usually in the arms, legs, or body cavities.
Rhabdomyosarcomas are malignant tumors that resemble developing skeletal muscle. These tumors most commonly grow in the arms or legs, but can also develop in the head or neck area, as well as the urinary and reproductive organs.
Synovial sarcomas are malignant tumors made up of cells that resemble the cells in joints. ("Synovial cells" line the joints.) However, synovial sarcomas do not necessarily arise in a joint, and the name is probably a misnomer, since the cancer cells are probably quite different from normal joint cells. Synovial sarcomas can arise in any location in the body, and they often appear in young adults.
Fibrosarcomas are cancer of the fibroblast-type cells in the body. Fibroblasts form scars and do other important connective functions. Fibrosarcomas often occur in tendons and ligaments (fibrous tissue), usually in the arms, legs, or trunk.
Fibrosarcomas are rare, accounting for fewer than 7% of primary malignant bone tumors. The five- and ten-year survival rates after radical surgery have been reported at 28% and 21.8%, respectively.
Chondrosarcomas are tumors of cells that form cartilage. Chondrosarcomas account for approximately 14% of malignant bone tumors. The incidence is greatest in individuals between 30 and 60 years of age, and among males. The most frequent sites of chondrosarcomas include the pelvic bone, long bones, scapula, and ribs. Less frequent sites include bones of the hand and foot, the nose, the maxilla, and the base of the skull. At present, chondrosarcomas remain nearly totally refractory to chemotherapeutic efforts inasmuch as chondrosarcomas usually have a poor blood supply. Consequently, drugs given intravenously generally do not reach the tumor in concentrations that are high enough to be therapeutically effective.
Malignant Fibrous Histiocytomas occur most commonly in the extremities (70-75%, with lower extremities accounting for 59%) of cases), followed by the retroperitoneum. Tumors typically arise in deep fascia or skeletal muscle.
Leiomyosarcomas are malignant tumors that develop from smooth muscle
\ tissue. They can arise anywhere in the body but the uterus or gastrointestinal tract are two relatively common locations.
In the majority of cases of soft-tissue sarcoma, no specific etio logic agent is identifiable. More commonly, an injury brings a preexisting neoplasm to the attention of the individual. However, a number of predisposing factors have been recognized.
Soft tissue sarcomas occur with greater frequency in patients with von Recklinghausen's disease (neurofibromatosis), Gardner's syndrome, Werner's syndrome, tuberous sclerosis, basal cell nevus syndrome, and among Li-Fraumeni kindreds (p53 mutations). The occurrences of bone tumors are also associated with hyperpara-thyroidism, chronic osteomyelitis, old bone infarct, osteochondromas, and enchondromas. 1-tnmunosuppressed patients such as renal transplant recipients and persons with autoimmunodeficiency syndrome (AIDS) have a higher risk for soft tissue sarcomas. Soft-tissue sarcomas have been reported to originate in radiation fields following therapeutic radiation for a variety of solid tumors. Exposure to various chemicals in specific occupations or situations has been linked with the development of soft-tissue sarcoma. These include the phenoxy acetic acids (forestry and agriculture workers), chlorophenols (sawmill workers), Thorotrast (diagnostic x-ray technicians), vinyl chloride (individuals working with this gas, used in making plastics and as a refrigerant), and arsenic (vineyard workers).
Soft-tissue sarcomas have been reported after previous exposure to alkylating chemotherapeutic agents, most commonly after treatment of pediatric acute lymphocytic leukemia.
Related conditions include Reactive pseudosarcomatous proliferans (non- neoplastic lesions that mimic sarcomas), nodular fascilitis (infiltrative or pseudosarcomatous fascilitis), proliferative fascilitis, proliferative myositis, myositis ossificans, malignant giant cell tumor, malignant lymphoma of bone (reticulum cell sarcoma), Ewing's tumor (Ewing's sarcoma) and Osteosarcoma (osteogenic sarcoma). Signs and symptoms of soft-tissue sarcoma depend, in large part, on the anatomic site of origin. Since 50% of soft-tissue sarcomas arise in an extremity, the majority of patients present with a palpable soft-tissue mass. Pain at presentation is noted in only one-third of cases. Because there are so many varied subtypes, and because their characteristics are so different, the risk and seriousness of soft-tissue sarcomas can vary widely. In some patients, sarcomas are minor, non-threatening tumors that can be cured with simple surgical excision. In others, the tumors can be large and much more aggressive, and require chemotherapy and radiation therapy as well as surgery. In addition, the capacity of sarcomas to metastasize to other sites also varies widely. If metastasis occurs, it can sometimes be cured with surgery, but at other times it can be a life-threatening problem. In general, bone and soft tissue tumors tend to involve contiguous tissue and muscle, and aggressively metastasize early to the lungs via the hematogenous route. Occasionally, soft tissue sarcomas can spread to regional lymph nodes.
The prognosis for patients with adult soft tissue sarcomas depends on several factors, including the patient's age and the size, histologic grade, and stage of the tumor. Factors associated with a poorer prognosis include age older than 60 years of age, tumors larger than 5 centimeters, or high-grade histology. While low-grade tumors are usually curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and the presence of hemorrhage and necrosis) are associated with higher local treatment failure rates and increased metastatic potential. Some histological subtypes such as rhabdomyosarcomas, synovial sarcomas, and malignant histiocytomas are considered poor prognosticators due to their high grade. If there is distant metastasis to the lymph nodes, lungs, or other bones, the prognosis is also lowered.
Standard treatment options include: Surgical excision, surgical excision with preoperative or postoperative radiation therapy, and if the tumor is unresectable, high- dose preoperative radiation therapy may be used, followed by surgical resection and postoperative radiation therapy. Today, doctors often give chemotherapy (Doxorubicin and ifosfamide) before surgery to patients with large, fast-growing sarcomas.
The development of advanced surgical techniques (e.g., microvascular tissue transfer, bone and joint replacement, and vascular reconstruction) and the application of multimodality approaches have allowed most patients to retain a functional extremity without any compromise in survival. Limb-sparing surgery employing adjuvant radiation to facilitate maximal local control has become the standard approach for large (T2) extremity soft-tissue sarcomas. In most centers, upwards of 90% of patients are treated with limb-sparing approaches. Amputation is reserved as a last resort option for local control, and is used with the knowledge that it does not affect survival.
Improved methods of diagnosis and prognosis of soft tissue sarcomas and effective treatment would be desirable. Accordingly, provided herein are methods that can be used in earlier diagnosis and prognosis of such cancers. Further provided are methods that can be used to screen candidate therapeutic agents for the ability to modulate, e.g., treat, them. Additionally provided herein are molecular targets and compositions for therapeutic intervention in these and other metastatic cancers.
SUMMARY OF THE INVENTION
The present invention provides compositions and methods for detecting or modulating soft tissue sarcoma associated sequences.
In one aspect, the invention provides a method of detecting a sarcoma cancer- associated transcript in a cell in a patient, the method comprising contacting a biological sample from the patient with a polynucleotide that selectively hybridized to a sequence at least 80% identical to a sequence as shown in Tables 1 A-l IC. hi one embodiment, the biological sample is a tissue sample, hi another embodiment, the biological sample comprises isolated nucleic acids, such as mRNA. In another embodiment, the method further comprises the step of amplifying nucleic acids before the step of contacting the biological sample with the polynucleotide. Often, the polynucleotide comprises a sequence as shown in the Tables. The polynucleotide can be labeled, e.g., with a fluorescent label and can be immobilized on a solid surface. In other embodiments the patient is undergoing a therapeutic regimen to treat a disease associated with these sarcomas or the patient is suspected of having a sarcoma-associated disorder.
In another aspect, the invention comprises an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in the Tables. The nucleic acid molecule can be labeled, e.g., with a fluorescent or radioactive label.
In other aspects, the invention provides an expression vector comprising an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in the Tables or a host cell comprising the expression vector.
In another aspect, the invention provides an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A-l IC. hi another embodiment, the invention provides an antibody that specifically binds a polypeptide which is encoded by a nucleotide sequence of the Tables. The antibody can be conjugated or fused to an effector component such as a fluorescent label, a toxin, or a radioisotope. In some embodiments, the antibody is an antibody fragment or a humanized antibody.
In another aspect, the invention provides a method of detecting a cell undergoing such a cancer in a biological sample from a patient, the method comprising contacting the biological sample with an antibody that specifically binds to a polypeptide encoded by a nucleotide sequence of Tables 1 A-l IC. In some embodiments, the antibody is further conjugated or fused to an effector component, e.g., a fluorescent label.
In another embodiment, the invention provides a method of detecting antibodies specific to a sarcoma in a patient, the method comprising contacting a biological sample from the patient with a polypeptide which is encoded by a nucleotide sequence of Tables lA-llC.
The invention also provides a method of identifying a compound that modulates the activity of a sarcoma-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a polypeptide encoded by a nucleotide sequence of Tables 1 A-l IC; and (ii) detecting an increase or a decrease in the activity of the polypeptide. In one embodiment, the polypeptide is encoded by a nucleotide sequence of Tables 1A-1 IC. In another embodiment, the polypeptide is expressed in a cell. The invention also provides a method of identifying a compound that modulates the sarcoma, the method comprising steps of: (i) contacting the compound with a cell undergoing such cancer; and (ii) detecting an increase or a decrease in the expression of a polypeptide encoded by a nucleotide sequence of the Tables. In one embodiment, the detecting step comprises hybridizing a nucleic acid sample from the cell with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in the Tables. In another embodiment, the method further comprises detecting an increase or decrease in the expression of a second sequence encoded by a nucleotide sequence of the Tables.
In another embodiment, the invention provides a method of inhibiting neoplastic properties in a cell that expresses a polypeptide at least 80% identical to a sequence encoded by a nucleotide sequence of Tables 1A-1 IC, the method comprising the step of contacting the cell with a therapeutically effective amount of an inhibitor of the polypeptide. hi one embodiment, the polypeptide is encoded by a nucleotide sequence of Tables 1A-1 IC. hi another embodiment, the inhibitor is an antibody.
Other aspects of the invention will become apparent by the following description of the invention.
Tables 1A-1 IC provide nucleotide sequence of genes that exhibit changes in expression levels as a function of time in tissue involved in cancer compared to normal or unaffected tissue.
DETAILED DESCRIPTION OF THE TABLES Table 1 A lists about 523 genes upregulated in chondrosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® (DNA microchip) array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
Table 2A lists about 763 genes upregulated in dermatofibrosarcoma protuberans relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
Table 3 A lists about 625 genes upregulated in fibrosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. Table 4A lists about 906 genes upregulated in liposarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. Table 5A lists about 595 genes upregulated in synovial sarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. Table 6A lists about 977 genes upregulated in rhabdomyosarcoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP " array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. Table 7 A lists about 973 genes upregulated in soft tissue sarcomas relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
Table 8 A lists about 712 genes upregulated in soft tissue sarcomas relative to normal soft tissues (muscle, skin, bone, adipose tissue). These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
Table 9A lists about 1078 genes upregulated in malignant fibrous histiocytoma relative to normal body tissues. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression.
Table 10A lists about 501 genes upregulated in soft tissue sarcoma relative to normal body tissues that are likely to encode proteins amenable to modulation by small molecules, peptides, or antibodies. These genes were selected from 59680 probesets on the Eos/Affymetrix Hu03 GENECHIP® array. Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression. The protein products of these genes often contain one or more domains indicative of have oncogenic function or of transducing intracellular signals, or of being modulatable by small molecules, peptides, or antibodies (e.g. pkinase, death-domain, 7tm, phosphatase, or ion_transporter). Certain predicted protein domains are noted. Tables 1B-1 IB list the accession numbers for those Pkey's lacking UnigenelD's for tables 1 A - 11 A, respectively. For each probeset we have listed the gene cluster number from which the oligonucleotides were designed. Gene clusters were compiled using sequences derived from Genbank ESTs and mRNAs. These sequences were clustered based on sequence similarity using Clustering and Alignment Tools (DoubleTwist, Oakland California). The Genbank accession numbers for sequences comprising each cluster are listed in the "Accession" column. Tables lC-1 IC list the genomic positioning for those Pkey's lacking Unigene ID's and accession numbers in tables 1 A-l 1 A, respectively. For each predicted exon, genomic sequence source used for prediction is also listed and cross-referenced. Nucleotide locations of each predicted exon are also listed.
DESCRIPTION OF THE SPECIFIC EMBODIMENTS In accordance with the objects outlined above, the present invention provides novel methods for diagnosis and prognosis evaluation for soft tissue sarcomas cancer (sometimes referred to herein as sarcoma disorders or STSD), as well as methods for screening for compositions which modulate those cancers or similar disorders. Also provided are methods for treating these cancers and related conditions. In particular, identification of markers selectively expressed on these cancers allows for use of that expression in diagnostic, prognostic, or therapeutic methods. As such, the invention defines various compositions, e.g., nucleic acids, polypeptides, antibodies, and small molecule agonists/antagonists, which will be useful to selectively recognize those markers. For example, therapeutic methods may take the form of protein therapeutics which use the marker expression for selective localization or modulation of function (for those markers which have a causative disease effect), for vaccines, identification of binding partners, or antagonism, e.g., using antisense or RNAi. The markers may be useful for molecular characterization of subsets of soft tissue sarcoma cancer or related diseases, which subsets may actually require very different treatments. Moreover, the markers may also be important in related diseases to the specific cancers, e.g., which affect similar tissues in non-malignant diseases, or have similar mechanisms of induction/maintenance. Metastatic processes or characteristics may also be targeted. Diagnostic and prognostic uses are made available, e.g., to subset related but distinct diseases, or to determine treatment strategy. The detection methods may be based upon nucleic acid, e.g., PCR or hybridization techniques, or protein, e.g., ELISA, imaging, IHC, etc. The diagnosis may be qualitative or quantitative, and may detect increases or decreases in expression levels.
Related conditions to these soft tissue sarcomas include, e.g., soft tissue tumors (e.g., fibrosarcoma, liposarcoma, leiomyosarcoma, histiocytoma, fibrohistiocytic sarcoma), smooth muscle tumors (e.g., rhabdomyoma, rhabdomyosarcoma) tumors of the blood and lymph vessels (e.g., angiosarcoma. lymphangiosarcoma, Kaposi's sarcoma), perivascular tumors (e.g., glomus tumors, hemangiopericytoma), synovial tumors (e.g., mesothelioma), neural tumors (e.g., neurofibroma, neurofibrosarcoma, malignant peripheral nerve sheath tumors, granular cell tumors, plexosarcoma, ganglioneuroblastoma, neuroepithelioma, extraskeletal Ewing's sarcoma, schwannoma, neuroma, ganglioneuroma), paraganglioma, extraskeletal cartilaginous and osseous tumors (e.g., chondrosarcoma, osteosarcoma), pluripotential mesenchymal tumors, epitheliod sarcomas, rhabdoid tumors, desmoplastic small cell tumors, and alveolar sarcomas. These markers may be similarly useful for addressing these related conditions, e.g., diagnosis, therapy, prognosis, etc.
Tables 1A-1 IC provide unigene cluster identification numbers for the nucleotide sequence of genes that exhibit increased or decreased expression in soft tissue sarcoma cancer samples. The tables also provide an exemplar accession number that provides a nucleotide sequence that is part of the unigene cluster.
Definitions The term "soft tissue sarcoma cancer protein" or "soft tissue sarcoma cancer polynucleotide" refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 92%, 94%, 96%, 97%, 98%, or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a unigene cluster of Tables 1A-1 IC; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence of Tables 1A-11C, and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to an anti-sense strand corresponding to a nucleic acid sequence of Tables 1 A-l IC and conservatively modified variants thereof; or (4) have an amino acid sequence that has greater than about 60% amino acid sequence identity, 65%, 70%, 75%, 80%, 85%, preferably 90%, 91%, 93%, 95%, 97%, 98%, or 99% or greater amino sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more amino acids, to an amino acid sequence encoded by a nucleotide sequence of or associated with a unigene cluster of Tables 1 A-l IC. A polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal. A "soft tissue sarcoma cancer polypeptide" and a "soft tissue sarcoma cancer polynucleotide," include both naturally occurring or recombinant forms.
A "full length" soft tissue sarcoma cancer protein or nucleic acid refers to a soft tissue sarcoma cancer polypeptide or polynucleotide sequence, or a variant thereof, that contains the elements normally contained in one or more naturally occurring, wild type soft tissue sarcoma cancer polynucleotide or polypeptide sequences. The "full length" may be prior to, or after, various stages of post- translation processing or splicing, including alternative splicing.
"Biological sample" as used herein is a sample of biological tissue or fluid that contains nucleic acids or polypeptides, e.g., of a cancer protein. Such samples include, but are not limited to, tissue isolated from primates, e.g., humans, or rodents, e.g., mice, and rats. Biological samples may also include sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histologic purposes. A biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish. Livestock and domestic animals are of interest.
"Providing a biological sample" means to obtain a biological sample for use in methods described in this invention. Most often, this will be done by removing a sample of cells from a mammal, such as a human or animal, but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose), or by performing the methods of the invention in vivo. Archival tissues, having treatment or outcome history, will be particularly useful. The terms "identical" or "percent identity," in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (e.g., about 70% identity, preferably 75%, 80%, 85%, 90%, 91%, 93%, 95%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site or the like). Such sequences are then said to be "substantially identical." This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and/or additions, as well as those that have substitutions. As described below, the algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Preferably, default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. A "comparison window", as used herein, includes reference to a segment of one of the number of contiguous positions selected from the group consisting of from about 20-600, usually about 50-200, more usually about 100-150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2:482-489, by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443-453, by the search for similarity method of Pearson and Lipman (1988) Proc. Nat Acad. Sci. USA 85:2444-2448, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Ausubel, et al. (eds. 1995 and supplements) Current Protocols in Molecular Biology Wiley). Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity include the BLAST and BLAST 2.0 algorithms, which are described in Altschul, et al. (1977) Nuc. Acids Res. 25:3389-3402; and Altschul, et al. (1990) J. Mol. Biol. 215:403-410. BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive- valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul, et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; ahyays > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Proc. Nat'l Acad. Sci. USA 89:10915-919) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands. The BLAST algorithm also performs a statistical analysis of the similarity between two sequences. See, e.g., Karlin and Altschul (1993) Proc. Nat'l Acad. Sci. USA 90:5873-5787. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001. Log values may be negative large numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc. An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, e.g., where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below. Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequences.
A "host cell" is a naturally occurring cell or a transformed cell that contains an expression vector and supports the replication or expression of the expression vector. Host cells may be cultured cells, explants, cells in vivo, and the like. Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or mammalian cells, e.g., CHO, HeLa, and the like (see, e.g., the American Type Culture Collection catalog).
The terms "isolated," "purified," or "biologically pure" refer to material that is substantially or essentially free from components that normally accompany it as found in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein or nucleic acid that is the predominant species present in a preparation is substantially purified. In particular, an isolated nucleic acid is separated from some open reading frames that naturally flank the gene and encode proteins other than protein encoded by the gene. The term "purified" in some embodiments denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. Preferably, it means that the nucleic acid or protein is at least about 85% pure, more preferably at least 95% pure, and most preferably at least 99%) pure. "Purify" or "purification" in other embodiments means removing at least one contaminant or component from the composition to be purified. In this sense, purification does not require that the purified compound be homogeneous, e.g., 100% pure.
The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers.
The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, e.g., an α carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.
Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
"Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode a given protein. For instance, the codons GCA, GCC, GCG, and GCU all encode the amino acid alanine. Thus, at a position where an alanine is specified by a codon, the codon can be altered to one of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. In certain contexts each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally similar molecule. Accordingly, a silent variation of a nucleic acid which encodes a polypeptide is implicit in a described sequence with respect to the expression product, but not necessarily with respect to actual probe sequences. As to amino acid sequences, it will be recognized that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds, or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" particularly where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention. Typically conservative substitutions include for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M). See, e.g., Creighton (1984) Proteins: Structure and Molecular Properties Freeman).
Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization, see, e.g., Alberts, et al. (eds. 2001) Molecular Biology of the Cell (4th ed.) Garland; and Cantor and Schimmel (1980) Biophysical Chemistry Part I: The Conformation of Biological Macromolecules Freeman. "Primary structure" refers to the amino acid sequence of a particular peptide. "Secondary structure" refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains. Domains are portions of a polypeptide that form a compact unit of the polypeptide and are typically 25 to approximately 500 amino acids long. Typical domains are made up of sections of lesser organization such as stretches of β-sheet and -helices. "Tertiary structure" refers to the complete three dimensional structure of a polypeptide monomer. "Quaternary structure" refers to the three dimensional structure formed, usually by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms. "Nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical equivalents used herein means at least two nucleotides covalently linked together. Oligonucleotides are typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50, or more nucleotides in length, up to about 100 nucleotides in length. Nucleic acids and polynucleotides are polymers, including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10,000, etc. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have at least one different linkage, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphophoroamidite linkages (see Eckstein (1992) Oligonucleotides and Analogues: A Practical Approach Oxford Univ. Press); and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in US Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7 of Sanghvi and Cook (eds. 1994) Carbohydrate Modifications in Antisense Research ACS Symposium Series 580. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.
A variety of references disclose such nucleic acid analogs, including, e.g., phosphoramidate (Beaucage, et al. (1993) Tetrahedron 49:1925-1963 and references therein; Letsinger (1970) J. Org. Chem. 35:3800-3803; Sprinzl, et al. (1977) Eur. J. Biochem. 81 :579-589; Letsinger, et al. (1986) Nuc. Acids Res. 14:3487-499; Sawai, et al. (1984) Chem. Lett. 805, Letsinger, et al. (1988) J. Am. Chem. Soc. 110:4470- 4471; and Pauwels, et al. (1986) Chemica Scripta 26:141-149), phosphorothioate (Mag, et al. (1991) Nuc. Acids Res. 19:1437-441; and US Patent No. 5,644,048), phosphorodithioate (Brill, et al. (1989) J. Am. Chem. Soc. 111:2321-322), O- methylphophoroamidite linkages (see Eckstein (1992) Oligonucleotides and
Analogues: A Practical Approach, Oxford Univ. Press), and peptide nucleic acid backbones and linkages (see Egholm (1992) J. Am. Chem. Soc. 114:1895-1897; Meier, et al. (1992) Chem. Int. Ed. Engl. 31:1008-1010; Nielsen (1993) Nature 365:566-568; and Carlsson, et al. (1996) Nature 380:207). Other analog nucleic acids include those with positive backbones (Denpcy, et al. (1995) Proc. Nat'l Acad. Sci. USA 92:6097-101); non-ionic backbones (US Patent Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141, and 4,469,863; Kiedrowski, et al. (1991) Angew. Chem. Intl. Ed. English 30:423-426; Letsinger, et al. (1988) J. Am. Chem. Soc. 110:4470-471; Jung, et al. (1994) Nucleoside and Nucleotide 13:1597-xxx; Chapters 2 and 3 in Sanghvi and Cook (eds. 1994) Carbohydrate Modifications in Antisense Research ACS Symposium Series 580; Mesmaeker, et al. (1994) Bioorganic and Medicinal Chem. Lett. 4:395-398; Jeffs, et al. (1994) J. Biomolecular NMR 34:17; and Horn, et al. (1996) Tetrahedron Lett. 37:743-xxx) and non-ribose backbones, including those described in US Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7 in Sanghvi and Cook (eds. 1994) Carbohydrate Modifications in Antisense Research ACS Symposium Series 580. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. See Jenkins, et al. (1995) Chem. Soc. Rev. pp 169-176. Several nucleic acid analogs are described in Rawls (page 35, June 2, 1997) C&E News.
Particularly useful are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs. These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in at least two advantages. The PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (Tm) for mismatched versus perfectly matched basepairs. DNA and
RNA typically exhibit a 2-4° C drop in Tm for an internal mismatch. With the non- ionic PNA backbone, the drop is closer to about 7-9° C. Similarly, due to their non- ionic nature, hybridization of the bases attached to these backbones is relatively insensitive to salt concentration, h addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. The depiction of a single strand also defines the sequence of the complementary strand; thus the sequences described herein also provide the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. "Transcript" typically refers to a naturally occurring RNA, e.g., a pre-mRNA, hnRNA, or mRNA. As used herein, the term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition, "nucleoside" includes non-naturally occurring analog structures. Thus, e.g., the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.
A "label" or a "detectable moiety" is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, physiological, chemical, or other physical means. Useful labels include 32ps fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins which can be made detectable, e.g., by incorporating a radiolabel into the peptide or used to detect antibodies specifically reactive with the peptide. The labels may be incoφorated into the soft tissue sarcoma cancer nucleic acids, proteins, and antibodies. Many methods known for conjugating the antibody to the label may be employed. See, e.g., Hunter, et al. (1962) Nature 144:945; David, et al. (1974) Biochemistry 13:1014-1021; Pain, et al. (1981) J. Immunol. Meth. 40:219-230; andNygren (1982) J. Histochem. and Cytochem. 30:407-412.
An "effector" or "effector moiety" or "effector component" is a molecule that is bound (or linked, or conjugated), either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds, to an antibody. The "effector" can be a variety of molecules including, e.g., detection moieties including radioactive compounds, fluorescent compounds, enzymes or substrates, tags such as epitope tags, toxins; activatable moieties, chemotherapeutic agents; chemoattractant or immunomodulating entities; lipases; antibiotics; or radioisotopes, e.g., emitting "hard" beta radiation.
A "labeled nucleic acid probe or oligonucleotide" is one that is bound, e.g., covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds to a label such that the presence of the probe may be detected by detecting the presence of the label bound to the probe. Alternatively, method using high affinity interactions may achieve the same results where one of a pair of binding partners binds to the other, e.g., biotin, streptavidin. As used herein a "nucleic acid probe or oligonucleotide" is a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (e.g., A, C, G, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in a probe may be joined by a linkage other than a phosphodiester bond, preferably one that does not functionally interfere with hybridization. Thus, e.g., probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages. Probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions. The probes are preferably directly labeled, e.g., with isotopes, chromophores, lumiphores, chromogens, or indirectly labeled, e.g., with biotin to which a streptavidin complex may later bind. By assaying for the presence or absence of the probe, one can detect the presence or absence of the select sequence or subsequence. Diagnosis or prognosis may be based at the genomic level, or at the level of RNA or protein expression.
The term "recombinant" when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein, or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, e.g., recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed, or not expressed. By the term "recombinant nucleic acid" herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid, e.g., using polymerases and endonucleases, in a form not normally found in nature. In this manner, operable linkage of different sequences is achieved. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, e.g., using the in vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non- recombinantly, are still considered recombinant for the purposes of the invention. Similarly, a "recombinant protein" is a protein made using recombinant techniques, e.g., through the expression of a recombinant nucleic acid as depicted above.
The term "heterologous" when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
A "promoter" is defined as an array of nucleic acid control sequences that direct transcription of a nucleic acid. As used herein, a promoter includes necessary nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element. A promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A "constitutive" promoter is a promoter that is active under most environmental and developmental conditions. An "inducible" promoter is a promoter that is active under environmental or developmental regulation. The term "operably linked" refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.
An "expression vector" is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell. The expression vector can be part of a plasmid, virus, or nucleic acid fragment. Typically, the expression vector includes a nucleic acid to be transcribed in operable linkage to a promoter.
The phrase "selectively (or specifically) hybridizes to" refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence under stringent hybridization conditions when that sequence is present in a complex mixture (e.g., total cellular or library DNA or RNA).
The phrase "stringent hybridization conditions" refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to essentially no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in "Overview of principles of hybridization and the strategy of nucleic acid assays" in Tijssen (1993) Hybridization with Nucleic Probes (Laboratory Techniques in Biochemistry and Molecular Biology) (vol. 24) Elsevier. Generally, stringent conditions are selected to be about 5-10° C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C for short probes (e.g., 10-50 nucleotides) and at least about 60° C for long probes (e.g., greater than about 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization. Exemplary stringent hybridization conditions can be as following: 50% formamide, 5x SSC, and 1% SDS, incubating at 42° C, or, 5x SSC, 1% SDS, incubating at 65° C, with wash in 0.2x SSC, and 0.1% SDS at 65° C. For PCR, a temperature of about 36° C is typical for low stringency amplification, although annealing temperatures may vary between about 32-48° C depending on primer length. For high stringency PCR amplification, a temperature of about 62° C is typical, although high stringency annealing temperatures can range from about 50-65° C, depending on the primer length and specificity. Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90-95° C for 30-120 sec, an annealing phase lasting 30-120 sec, and an extension phase of about 72° C for 1-2 min. Protocols and guidelines for low and high stringency amplification reactions are provided, e.g., in Innis, et al. (1990) PCR Protocols: A Guide to Methods and Applications, Academic Press, NY. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions.
Exemplary "moderately stringent hybridization conditions" include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37° C, and a wash in IX SSC at 45° C. A positive hybridization is typically at least twice background. Alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous references, e.g., Ausubel, et al. (eds. 1991 and supplements) Current Protocols in Molecular Biology Wiley.
The phrase "functional effects" in the context of assays for testing compounds that modulate activity of a soft tissue sarcoma cancer protein includes the determination of a parameter that is indirectly or directly under the influence of the cancer protein, e.g., a physiological, functional, physical, or chemical effect, such as the ability to increase or decrease soft tissue sarcoma cancer. It includes ligand binding activity; cell viability; cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis; and other characteristics of cancer cells. "Functional effects" include in vitro, in vivo, and ex vivo activities.
By "determining the functional effect" is meant assaying for a compound that increases or decreases a parameter that is indirectly or directly under the influence of a soft tissue sarcoma cancer protein sequence, e.g., physiological, functional, enzymatic, physical, or chemical effects. Such functional effects can be measured, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility properties for the protein, measuring inducible markers or transcriptional activation of the cancer protein; measuring binding activity or binding assays, e.g., binding to antibodies or other ligands, and measuring growth, cellular proliferation, cell viability, cellular transformation, growth factor or serum dependence, tumor specific marker levels, invasiveness into Matrigel, tumor growth and metastasis in vivo, mRNA and protein expression, and other characteristics of cancer cells. The functional effects can be evaluated by many means, e.g., microscopy for quantitative or qualitative measures of alterations in morphological features, measurement of RNA stability, identification of downstream or reporter gene expression (CAT, luciferase, β-gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, inducible markers, and ligand binding assays.
"Inhibitors", "activators", and "modulators" of soft tissue sarcoma cancer polynucleotide and polypeptide sequences are used to refer to activating, inhibitory, or modulating molecules identified using in vitro and in vivo assays of cancer polynucleotide and polypeptide sequences. Inhibitors are compounds that, e.g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of soft tissue sarcoma cancer proteins, e.g., antagonists. "Activators" are compounds that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate soft tissue sarcoma cancer protein activity. Inhibitors, activators, or modulators also include genetically modified versions of soft tissue sarcoma cancer proteins, e.g., versions with altered activity, as well as naturally occurring and synthetic ligands, antagonists, agonists, antibodies, small chemical molecules and the like. Such assays for inhibitors and activators include, e.g., expressing the cancer protein in vitro, in cells, or cell membranes, applying putative modulator compounds, and then determining the functional effects on activity, as described above. Activators and inhibitors of soft tissue sarcoma cancer can also be identified by incubating cancer cells with the test compound and determining increases or decreases in the expression of 1 or more soft tissue sarcoma cancer proteins, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more cancer proteins, such as soft tissue sarcoma cancer proteins comprising the sequences set out in the Tables.
Samples or assays comprising soft tissue sarcoma cancer proteins that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of inhibition. Control samples (untreated with inhibitors) are assigned a relative protein activity value of 100%. Inhibition of a polypeptide is achieved when the activity value relative to the control is about 80%, preferably 50%, more preferably 25-0%0. Activation of a soft tissue sarcoma cancer polypeptide is achieved when the activity value relative to the control (untreated with activators) is 110%, more preferably 150%, more preferably about 200-500%) (e.g., two to five fold higher relative to the control), more preferably 1000-3000%) higher.
The phrase "changes in cell growth" refers to a change in cell growth or proliferation characteristics in vitro or in vivo, such as cell viability, formation of foci, anchorage independence, semi-solid or soft agar growth, changes in contact inhibition and density limitation of growth, loss of growth factor or serum requirements, changes in cell morphology, gaining or losing immortalization, gaining or losing tumor specific markers, ability to form or suppress tumors when injected into suitable animal hosts, and/or immortalization of the cell. See, e.g., pp. 231-241 in Freshney (1994) Culture of Animal Cells a Manual of Basic Technique (2d ed.) Wiley-Liss. "Tumor cell" refers to precancerous, cancerous, and normal cells in a tumor. "Cancer cells," "transformed" cells or "transformation" in tissue culture, refers to spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material. Although transformation can arise from infection with a transforming virus and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation is associated with phenotypic changes, such as immortalization of cells, aberrant growth control, nonmorphological changes, and/or malignancy. See, Freshney (2001) Culture of Animal Cells: A Manual of Basic Technique (4th ed.) Wiley-Liss.
"Antibody" refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively. Typically, the antigen-binding region of an antibody will be most critical in specificity and affinity of binding. See Paul (ed. 1999) Fundamental Immunology (4th ed.) Raven.
An exemplary immunoglobulin (antibody) structural unit comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light" (about 25 kD) and one "heavy" chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100-110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VjJ and variable heavy chain (VJJ) refer to these light and heavy chains respectively.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well- characterized fragments produced by digestion with various peptidases. Thus, e.g., pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab)'2, a dimer of Fab which itself is a light chain joined to Vjj-Cjjl by a disulfide bond. The F(ab)'2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F(ab)'2 dimer into an Fab' monomer. The Fab' monomer is essentially Fab with part of the hinge region. See Paul (ed. 1999) Fundamental Immunology (4th ed.) Raven. While various antibody fragments are defined in terms of the digestion of an intact antibody, it will be appreciated that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, also includes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (e.g., McCafferty, et al. (1990) Nature 348:552-554).
For preparation of antibodies, e.g., recombinant, monoclonal, or polyclonal antibodies, many techniques can be used. See, e.g., Kohler and Milstein (1975) Nature 256:495-497; Kozbor, et al. (1983) Immunology Today 4:72; Cole, et al. (1985) pp. 77-96 in Reisfeld and Sell (1985) Monoclonal Antibodies and Cancer Therapy Liss; Coligan (1991) Current Protocols in Immunology Lippincott; Harlow and Lane (1988) Antibodies: A Laboratory Manual CSH Press; and Goding (1986) Monoclonal Antibodies: Principles and Practice (2d ed.) Academic Press. Techniques for the production of single chain antibodies (US Patent 4,946,778) can be adapted to produce antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms such as other mammals, may be used to express humanized antibodies. Alternatively, phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to selected antigens. See, e.g., McCafferty, et al. (1990) Nature 348:552-554; Marks, et al. (1992) Biotechnology 10:779-783. A "chimeric antibody" is an antibody molecule in which (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule wliich confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.
Identification, Expression of soft tissue sarcoma cancer-associated sequences In one aspect, the expression levels of genes are determined in different patient samples for which diagnosis information is desired, to provide expression profiles. An expression profile of a particular sample is essentially a "fingerprint" of the state of the sample; while two states may have a particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. That is, normal tissue may be distinguished from sarcoma disorder tissue. By comparing expression profiles of tissue in known different soft tissue sarcoma cancer states, e.g., stages or disease course outcomes, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained. Molecular profiling may distinguish subtypes of a currently collective disease designation, e.g., different forms of cancer processes.
The identification of sequences that are differentially expressed in cancer versus non-cancer tissue allows the use of this information in a number of ways. For example, a particular treatment regime may be evaluated: does a chemotherapeutic drug act to down-regulate soft tissue sarcoma cancer, and thus tumor growth or recurrence, in a particular patient. Alternatively, a treatment step may induce other markers which may be used as targets to destroy tumor cells. Similarly, diagnosis and treatment outcomes may be done or confirmed by comparing patient samples with the known expression profiles. Cancer tissue can be compared to non-cancerous conditions, or be analyzed to determine the stage of soft tissue sarcoma cancer in the tissue, or origin of primary tumor, e.g., metastasis from a remote primary site. Furthermore, these gene expression profiles (or individual genes) allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; e.g., screening can be done for drugs that suppress the cancer expression profile. This may be done by making biochips comprising sets of the important soft tissue sarcoma cancer genes, which can then be used in these screens. These methods can also be done on the protein basis; that is, protein expression levels of the cancer proteins can be evaluated for diagnostic purposes or to screen candidate agents. In addition, the cancer nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the cancer proteins (including antibodies and other modulators thereof) admimstered as therapeutic drugs.
Thus the present invention provides nucleic acid and protein sequences that are differentially expressed in soft tissue sarcoma cancer relative to normal tissues and/or non-malignant disease, or in different types of related diseases, herein termed "soft tissue sarcoma cancer sequences". As outlined below, soft tissue sarcoma cancer sequences include those that are up-regulated (e.g., expressed at a higher level) in disorders associated with soft tissue sarcoma cancer, as well as those that are down- regulated (e.g., expressed at a lower level). In one embodiment, the soft tissue sarcoma cancer sequences are from humans; however, as will be appreciated, soft tissue sarcoma cancer sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other soft tissue sarcoma cancer sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc) and pets (e.g., dogs, cats, etc.). Soft tissue sarcoma cancer sequences from other organisms may be obtained using the techniques outlined below.
Soft tissue sarcoma cancer sequences can include both nucleic acid and amino acid sequences. In one embodiment, the soft tissue sarcoma cancer sequences are recombinant nucleic acids. These nucleic acid sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes or PCR microtiter plates with selected probes to the soft tissue sarcoma cancer sequences. A soft tissue sarcoma cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, e.g., using homology programs or hybridization conditions. For identifying soft tissue sarcoma cancer-associated sequences, the cancer screen typically includes comparing genes identified in different tissues, e.g., normal and cancer tissues, cancer and non-malignant conditions, non-malignant conditions and normal tissues, or tumor tissue samples from patients who have metastatic disease vs. non metastatic tissue. Other suitable tissue comparisons include comparing cancer samples with metastatic cancer samples from other cancers, such as lung, stomach, gastrointestinal cancers, etc. Samples of different stages of cancer, e.g., survivor tissue, drug resistant states, and tissue undergoing metastasis, are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated for the preparation of mRNA. Suitable biochips are commercially available, e.g., from Affymetrix, Santa Clara, CA. Gene expression profiles as described herein are generated and the data analyzed.
In one embodiment, the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, and not limited to lung, heart, brain, liver, stomach, kidney, muscle, colon, small intestine, large intestine, spleen, bone, and/or placenta, h another embodiment, those genes identified during the cancer screen that are expressed in a significant amount in other tissues (e.g., essential organs) are removed from the profile, although in some embodiments, this is not necessary (e.g., where organs may be dispensable, e.g., female or male specific). That is, when screening for drugs, it is usually preferable that the target expression be disease specific, to minimize possible side effects on other organs were there expression.
In one embodiment, soft tissue sarcoma cancer sequences are those that are up-regulated in soft tissue sarcoma cancer; that is, the expression of these genes is higher in the cancer tissue as compared to non-cancer or non-malignant tissue. "Upregulation" as used herein often means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred. Another embodiment is directed to sequences up-regulated in non-malignant conditions relative to normal. Uniformity among relevant samples is desired. Unigene cluster identification numbers and accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. GenBank is available, see, e.g., Benson, et al. (1998) Nuc. Acids Res. 26:1-7. Sequences are also available in other databases, e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ). In some situations, the sequences may be derived from assembly of available sequences or be predicted from genomic DNA using exon prediction algorithms, such as FGENESH. See Salamov and Solovyev (2000) Genome Res. 10:516-522. In other situations, sequences have been derived from cloning and sequencing of isolated nucleic acids.
In another embodiment, soft tissue sarcoma cancer sequences are those that are down-regulated in cancer; that is, the expression of these genes is lower compared to non-cancer tissue. "Down-regulation" as used herein often means at least about a two-fold change, preferably at least about a three fold change, with at least about five- fold or higher being useful.
By the term "recombinant nucleic acid" herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid e.g., using polymerases and endonucleases, in a form not normally found in nature. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, e.g., using the in vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention.
Similarly, a "recombinant protein" is a protein made using recombinant techniques, e.g., through the expression of a recombinant nucleic acid as depicted above. A recombinant protein is distinguished from naturally occurring protein by at least one or more characteristics. The protein may be isolated or purified away from ' some or most of the proteins and compounds with which it is normally associated in its wild type host, and thus may be substantially pure. An isolated protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, preferably constituting at least about 0.5%, more preferably at least about 5% by weight of the total protein in a given sample. A substantially pure protein comprises at least about 75% by weiglit of the total protein, with at least about 80% being preferred, and at least about 90% being particularly preferred. The definition includes the production of a soft tissue sarcoma cancer protein from one organism in a different organism or host cell. Alternatively, the protein may be made at a significantly higher concentration than is normally seen, through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels. Alternatively, the protein may be in a form not normally found in nature, as in the addition of an epitope tag or amino acid substitutions, insertions and deletions, as discussed below.
In one embodiment, the soft tissue sarcoma cancer sequences are nucleic acids. Soft tissue sarcoma cancer sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes to the cancer sequences can be generated. In the broadest sense, then, by "nucleic acid" or "oligonucleotide" or grammatical equivalents herein means at least two nucleotides covalently linked together. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have alternate backbones, comprising, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphophoroamidite linkages (see Eckstein (1992) Oligonucleotides and Analogues: A Practical Approach, Oxford Univ. Press); and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in US Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7 in Sanghvi and Cook (eds. 1994) Carbohydrate Modifications in Antisense Research ACS Symposium Series 580. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip.
Nucleic acid analogs may find use in the present invention. In addition, mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. Particularly useful are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs. These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages. First, the PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (Tm) for mismatched versus perfectly matched basepairs. DNA and RNA typically exhibit a 2-4° C drop in Tm for an internal mismatch. With the non- ionic PNA backbone, the drop is closer to 7-9° C. Similarly, due to their non-ionic nature, hybridization of the bases attached to these backbones is relatively insensitive to salt concentration. In addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. The depiction of a single strand also defines the sequence of a complementary strand; thus the sequences described herein also provide the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. As used herein, the term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition, "nucleoside" includes non-naturally occurring analog structures. Thus, e.g., the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside. A soft tissue sarcoma cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the soft tissue sarcoma cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
For identifying soft tissue sarcoma cancer-associated sequences, the cancer screen typically includes comparing genes identified in cancer cells with genes identified in controls. Samples of normal tissue and tissue associated with soft tissue sarcoma cancer are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated for the preparation of mRNA. Suitable biochips are commercially available, e.g., from Affymetrix. Gene expression profiles as described herein are generated and the data analyzed.
In one embodiment, the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, but not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone, and placenta. In another embodiment, those genes identified during the cancer screen that are expressed in significant amount in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drugs, it is usually preferable that the target be disease specific, to minimize possible side effects.
In one embodiment, soft tissue sarcoma cancer sequences are those that are up-regulated in soft tissue sarcoma cancer disorders; that is, the expression of these genes is higher in the disease tissue as compared to normal tissue. "Up-regulation" as used herein means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred. Accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. See, e.g., Benson, et al. (1998) Nuc. Acids Res. 26:1-7. Sequences are also available in other databases, e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ). In addition, most genes were found to be expressed in a limited amount or not at all in heart, brain, lung, liver, breast, kidney, prostate, small intestine, and spleen.
In another embodiment, soft tissue sarcoma cancer sequences are those that are down-regulated in the soft tissue sarcoma cancer disorder; that is, the expression of these genes is lower in cancer tissue as compared to normal tissue. "Down- regulation" as used herein means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred.
Informatics The ability to identify genes that undergo changes in expression with time during soft tissue sarcoma cancer can additionally provide high-resolution, high- sensitivity datasets which can be used in the areas of diagnostics, therapeutics, drug development, biosensor development, and other related areas. For example, the expression profiles can be used in diagnostic or prognostic evaluation of patients with soft tissue sarcoma cancer-associated disease. Or as another example, subcellular toxicological information can be generated to better direct drug structure and activity correlation. See Anderson (June 11-12, 1998) Pharmaceutical Proteomics: Targets, Mechanism, and Function, paper presented at the IBC Proteomics conference, Coronado, CA. Subcellular toxicological information can also be utilized in a biological sensor device to predict the likely toxicological effect of chemical exposures and likely tolerable exposure thresholds (see, US Patent No. 5,811,231). Similar advantages accrue from datasets relevant to other biomolecules and bioactive agents (e.g., nucleic acids, saccharides, lipids, drugs, and the like). Thus, in another embodiment, the present invention provides a database that includes at least one set of data assay data. The data contained in the database is acquired , e.g., using array analysis either singly or in a library format. The database can be in a form in which data can be maintained and transmitted, but is preferably an electronic database. The electronic database of the invention can be maintained on an electronic device allowing for the storage of and access to the database, such as a personal computer, but is preferably distributed on a wide area network, such as the World Wide Web.
The focus of the present section on databases that include peptide sequence data is for clarity of illustration only. Similar databases can be assembled for assay data acquired using an assay of the invention.
The compositions and methods for identifying and/or quantitating the relative and/or absolute abundance of a variety of molecular and macromolecular species from a biological sample exhibiting soft tissue sarcoma cancer, e.g., the identification of soft tissue sarcoma cancer-associated sequences described herein, provide an abundance of information, which can be correlated with pathological conditions, predisposition to disease, drug testing, therapeutic monitoring, gene-disease causal linkages, identification of correlates of immunity and physiological status, among others. Although the data generated from the assays of the invention is suited for manual review and analysis, prior data processing using high-speed computers may be utilized.
An array of methods for indexing and retrieving biomolecular information is available. For example, US Patents 6,023,659 and 5,966,712 disclose a relational database system for storing biomolecular sequence information in a manner that allows sequences to be catalogued and searched according to one or more protein function hierarchies. US Patent 5,953,727 discloses a relational database having sequence records containing information in a format that allows a collection of partial-length DNA sequences to be catalogued and searched according to association with one or more sequencing projects for obtaining full-length sequences from the collection of partial length sequences. US Patent 5,706,498 discloses a gene database retrieval system for making a retrieval of a gene sequence similar to a sequence data item in a gene database based on the degree of similarity between a key sequence and a target sequence. US Patent 5,538,897 discloses a method using mass spectroscopy fragmentation patterns of peptides to identify amino acid sequences in computer databases by comparison of predicted mass spectra with experimentally-derived mass spectra using a closeness-of-fit measure. US Patent 5,926,818 discloses a multidimensional database comprising a functionality for multi-dimensional data analysis described as on-line analytical processing (OLAP), which entails the consolidation of projected and actual data according to more than one consolidation path or dimension. US Patent 5,295,261 reports a hybrid database structure in which the fields of each database record are divided into two classes, navigational and informational data, with navigational fields stored in a hierarchical topological map which can be viewed as a tree structure or as the merger of two or more such tree structures. See also Mount (2001) Bioinformatics: Sequence and Genome Analysis CSH Press, NY; Durbin, et al. (eds. 1999) Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids Cambridge Univ. Press; Baxevanis and Oeullette (eds. 1998) Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins (2d ed.) Wiley-Liss; Rashidi and Buehler (1999) Bioinformatics: Basic Applications in Biological Science and Medicine CRC Press; Setubal, et al. (eds. 1997) Introduction to Computational Molecular Biology Brooks/Cole; Misener and Krawetz (eds. 2000) Bioinformatics: Methods and Protocols Humana Press; Higgins and Taylor (eds. 2000) Bioinformatics: Sequence, Structure, and Databanks: A Practical Approach Oxford Univ. Press; Brown (2001) Bioinformatics: A Biologist's Guide to Biocomputing and the Internet Eaton Pub.; Han and Kamber (2000) Data Mining: Concepts and Techniques Kauftnann Pub.; and Waterman (1995) Introduction to Computational Biology: Maps, Sequences, and Genomes Chap and Hall.
The present invention provides a computer database comprising a computer and software for storing in computer-retrievable form assay data records cross- tabulated, e.g., with data specifying the source of the target-containing sample from which each sequence specificity record was obtained.
In an exemplary embodiment, at least one of the sources of target-containing sample is from a control tissue sample known to be free of pathological disorders. In a variation, at least one of the sources is a known pathological tissue specimen, e.g., a neoplastic lesion or another tissue specimen to be analyzed for soft tissue sarcoma cancer, hi another variation, the assay records cross-tabulate one or more of the following parameters for each target species in a sample: (1) a unique identification code, which can include, e.g., a target molecular structure and/or characteristic separation coordinate (e.g., electrophoretic coordinates); (2) sample source; and (3) absolute and/or relative quantity of the target species present in the sample.
The invention also provides for the storage and retrieval of a collection of target data in a computer data storage apparatus, which can include magnetic disks, optical disks, magneto-optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic bubble memory devices, and other data storage devices, including CPU registers and on-CPU data storage arrays. Typically, the target data records are stored as a bit pattern in an array of magnetic domains on a magnetizable medium or as an array of charge states or transistor gate states, such as an array of cells in a DRAM device (e.g., each cell comprised of a transistor and a charge storage area, which may be on the transistor). In one embodiment, the invention provides such storage devices, and computer systems built therewith, comprising a bit pattern encoding a protein expression fingerprint record comprising unique identifiers for at least 10 target data records cross-tabulated with target source.
When the target is a peptide or nucleic acid, the invention preferably provides a method for identifying related peptide or nucleic acid sequences, comprising performing a computerized comparison between a peptide or nucleic acid sequence assay record stored in or retrieved from a computer storage device or database and at least one other sequence. The comparison can include a sequence analysis or comparison algorithm or computer program embodiment thereof (e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison may be of the relative amount of a peptide or nucleic acid sequence in a pool of sequences determined from a polypeptide or nucleic acid sample of a specimen.
The invention also may provide a magnetic disk, such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, AIX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing in a computerized sequence analysis, comparison, or relative quantitation method.
The invention also provides a network, comprising a plurality of computing devices linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone line, ISDN line, wireless network, optical fiber, or other suitable signal transmission medium, whereby at least one network device (e.g., computer, disk array, etc.) comprises a pattern of magnetic domains (e.g., magnetic disk) and/or charge domains (e.g., an array of DRAM cells) composing a bit pattern encoding data acquired from an assay of the invention.
The invention also provides a method for transmitting assay data that includes generating an electronic signal on an electronic communications device, such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
In one embodiment, the invention provides a computer system for comparing a query target to a database containing an array of data structures, such as an assay result obtained by the method of the invention, and ranking database targets based on the degree of identity and gap weight to the target data. A central processor is initialized to load and execute the computer program for alignment and/or comparison of the assay results. Data for a query target is entered into the central processor via an I/O device. Execution of the computer program results in the central processor retrieving the assay data from the data file, which comprises a binary description of an assay result.
The target data or record and the computer program can be transfened to secondary memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or SDRAM). Targets are ranked according to the degree of coπespondence between a selected assay characteristic (e.g., binding to a selected affinity moiety) and the same characteristic of the query target and results are output via an I/O device. For example, a central processor can be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000, SPARC, MIPS 4400, MIPS 10000, VAX, etc.); a program can be a commercial or public domain molecular biology software package (e.g., UWGCG Sequence Analysis Software, Darwin); a data file can be an optical or magnetic disk, a data server, a memory device (e.g., DRAM, SRAM, SGRAM, SDRAM, EPROM, bubble memory, flash memory, etc.); an I/O device can be a terminal comprising a video display and a keyboard, a modem, an ISDN terminal adapter, an Ethernet port, a punched card reader, a magnetic strip reader, or other suitable I/O device. The invention also provides the use of a computer system, such as that described above, which comprises: (1) a computer; (2) a stored bit pattern encoding a collection of peptide sequence specificity records obtained by the methods of the invention, which may be stored in the computer; (3) a comparison target, such as a query target; and (4) a program for alignment and comparison, typically with rank- ordering of comparison results on the basis of computed similarity values.
Soft tissue sarcoma cancer-associated sequences
Soft tissue sarcoma cancer proteins of the present invention maybe classified as secreted proteins, transmembrane proteins, or intracellular proteins. In one embodiment, the soft tissue sarcoma cancer protein is an intracellular protein. Intracellular proteins may be found in the cytoplasm and/or in the nucleus or associated with the intracellular side of the plasma membrane. Intracellular proteins are involved in all aspects of cellular function and replication (including, e.g., signaling pathways); abenant expression of such proteins often results in unregulated or disregulated cellular processes. See, e.g., Alberts, et al. (eds. 1994) Molecular Biology of the Cell (3d ed.) Garland. For example, many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity, and the like. Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles.
An increasingly appreciated concept in characterizing proteins is the presence in the proteins of one or more motifs for which defined functions have been attributed. In addition to the highly conserved sequences found in the enzymatic domain of proteins, highly conserved sequences have been identified in proteins that are involved in protein-protein interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner. PTB domains, which are distinct from SH2 domains, also bind tyrosine phosphorylated targets. SH3 domains bind to proline-rich targets. In addition, PH domains, tetratricopeptide repeats and WD domains to name only a few, have been shown to mediate protein-protein interactions. Some of these may also be involved in binding to phospholipids or other second messengers. These motifs can be identified on the basis of amino acid sequence; thus, an analysis of the sequence of proteins may provide insight into both the enzymatic potential of the molecule and/or molecules with which the protein may associate. One useful database is Pfam (protein families), which is a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains. Versions are available via the 5. internet from Washington University in St. Louis, the Sanger Center in England, and the Karolinska Institute in Sweden. See, e.g., Bateman, et al. (2000) Nuc. Acids Res. 28:263-266; Sonnhammer, et al. (1997) Proteins 28:405-420; Bateman, et al. (1999) Nuc. Acids Res. 27:260-262; and Sonnhammer, et al. (1998) Nuc. Acids Res. 26:320- 322. 0 In another embodiment, the cancer sequences are transmembrane proteins.
Transmembrane proteins are molecules that span a phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular 5 domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles. For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains, h addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins. 0 Transmembrane proteins may contain from one to many transmembrane domains. For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/threonine protein kinases contain a single transmembrane domain. However, various other proteins including channels and adenylyl cyclases contain numerous transmembrane domains. Many important cell 5 surface receptors such as G protein coupled receptors (GPCRs) are classified as "seven transmembrane domain" proteins, as they contain 7 membrane spanning regions. Characteristics of transmembrane domains include approximately 20 consecutive hydrophobic amino acids that may be followed or flanked by charged amino acids. Therefore, upon analysis of the amino acid sequence of a particular 0 protein, the localization and number of transmembrane domains within the protein may be predicted. Important transmembrane protein receptors include, but are not limited to the insulin receptor, insulin-like growth factor receptor, human growth hormone receptor, glucose transporters, transferrin receptor, epidermal growth factor receptor, low density lipoprotein receptor, epidermal growth factor receptor, leptin receptor, and interleukin receptors, e.g., IL-1 receptor, IL-2 receptor, etc.
The extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains. Conserved structure and/or functions have been ascribed to different extracellular motifs. Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are found on receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF, and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, neurotrophic factors and the like. Extracellular domains also bind to cell- associated molecules. In this respect, they mediate cell-cell interactions. Cell- associated ligands can be tethered to the cell, e.g., via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins. Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
Soft tissue sarcoma cancer proteins that are transmembrane are useful in the present invention as they are readily accessible targets for immunotherapeutics, as are described herein. In addition, as outlined below, transmembrane proteins can be also useful in imaging modalities. Antibodies may be used to label such readily accessible proteins in situ. Alternatively, antibodies can also label intracellular proteins, in which case samples are typically permeabilized to provide access to intracellular proteins, hi addition, some membrane proteins can be processed to release a soluble protein, or to expose a residual fragment. Released soluble proteins may be useful diagnostic markers, processed residual protein fragments may be useful markers of neoplastic disease.
A transmembrane protein can be made soluble by removing transmembrane sequences, e.g., through recombinant methods. Furthermore, transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
In another embodiment, the cancer proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway. Secreted proteins are involved in numerous physiological events; e.g., if circulating, they often serve to transmit signals to various other cell types. Secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor), an endocrine manner (acting on cells at a distance, e.g., secretion into the blood stream), or exocrine (secretion, e.g., through a duct or to adjacent epithelial surface as sweat glands, sebaceous glands, pancreatic ducts, lacrimal glands, mammary glands, wax producing glands of the ear, etc.). Thus secreted molecules often find use in modulating or altering numerous aspects of physiology. Soft tissue sarcoma cancer proteins that are secreted proteins are included in the present invention as they serve as good targets for diagnostic markers, e.g., for blood, plasma, serum, or stool tests. Those which are enzymes may be antibody or small molecule targets. Others may be useful as vaccine targets, e.g., via CTL mechanisms.
Soft tissue sarcoma cancer-associated nucleic acids
A soft tissue sarcoma cancer sequence is typically initially identified by substantial nucleic acid and/or amino acid sequence homology or linkage to the cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions. Typically, linked sequences on a mRNA are found on the same molecule.
As detailed elsewhere, percent identity can be determined using an algorithm such as BLAST. One method utilizes the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively. Alignment may include the introduction of gaps in the sequences to be aligned. In addition, for sequences which contain either more or fewer nucleotides than those of the nucleic acids described, the percentage of homology may be determined based on the number of homologous nucleosides in relation to the total number of nucleosides. Thus, e.g., homology of sequences shorter than those of the sequences identified will be determined using the number of nucleosides in the shorter sequence.
In one embodiment, the nucleic acid homology is determined through hybridization studies. Thus, e.g., nucleic acids which hybridize under high stringency to a nucleic acid of Tables 1 A-l IC, or its complement, or is also found on naturally occurring mRNAs is considered a soft tissue sarcoma cancer sequence. In another embodiment, less stringent hybridization conditions are used; e.g., moderate or low stringency conditions may be used; see Ausubel, supra, and Tijssen, supra.
The soft tissue sarcoma cancer nucleic acid sequences of the invention, e.g., the sequences in Tables 1A-1 IC, can be fragments of larger genes, e.g., they are nucleic acid segments. "Genes" in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, using the sequences provided herein, extended sequences, in either direction, of the cancer genes can be obtained, using techniques well known for cloning either longer sequences or the full length sequences; see Ausubel, et al., supra. Much can be done by informatics and many sequences can be clustered to include multiple sequences, e.g., systems such as UniGene.
Once the soft tissue sarcoma cancer nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire cancer nucleic acid coding regions or the entire mRNA sequence. Once isolated from its natural source, e.g., contained within a plasmid or other vector or excised therefrom as a linear nucleic acid segment, the recombinant cancer nucleic acid can be further-used as a probe to identify and isolate other soft tissue sarcoma cancer nucleic acids, e.g., extended coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant cancer nucleic acids and proteins.
The soft tissue sarcoma cancer nucleic acids of the present invention are used in several ways. In one embodiment, nucleic acid probes to the cancer nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, e.g., for gene therapy, vaccine, and/or antisense applications. Alternatively, cancer nucleic acids that include coding regions of cancer proteins can be put into expression vectors for the expression of cancer proteins, again for screening purposes or for administration to a patient.
In another embodiment, nucleic acid probes to soft tissue sarcoma cancer nucleic acids (both the nucleic acid sequences outlined in the figures and/or the complements thereof) are made. The nucleic acid probes attached to the biochip are designed to be substantially complementary to cancer nucleic acids, e.g., the target sequence (either the target sequence of the sample or to other probe sequences, e.g., in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs. As outlined below, this complementarity need not be perfect; there may be a number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention. However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence. Thus, by "substantially complementary" herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under normal reaction conditions, particularly high stringency conditions, as outlined herein.
A nucleic acid probe is generally single stranded but can be partially single and partially double stranded. The strandedness of the probe is dictated by the structure, composition, and properties of the target sequence. In general, the nucleic acid probes range from about 8-100 bases long, with from about 10-80 bases being prefened, and from about 30-50 bases being particularly prefened. That is, generally whole genes are not used. In some embodiments, much longer nucleic acids can be used, up to hundreds of bases.
In one embodiment, more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That is, two, three, four, or more probes, with three being prefened, are used to build in a redundancy for a particular target. The probes can be overlapping (e.g., have some sequence in common), or separate. In some cases, PCR primers may be used to amplify signal for higher sensitivity.
Nucleic acids can be attached or immobilized to a solid support in a wide variety of ways. By "immobilized" and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined. The binding can typically be covalent or non-covalent. By "non-covalent binding" and grammatical equivalents herein is meant one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non- covalent binding of the biotinylated probe to the streptavidin. By "covalent binding" and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.
In general, the probes are attached to the biochip in a wide variety of ways. As described herein, the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip.
The biochip comprises a suitable solid substrate. By "substrate" or "solid support" or other grammatical equivalents herein is meant a material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. Often, the substrate may contain discrete individual sites appropriate for individual partitioning and identification. The number of possible substrates is very large, and includes, but is not limited to, glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc. In general, the substrates allow optical detection and do not appreciably fluoresce. See WO 00/55627. Generally the substrate is planar, although other configurations of substrates may be used as well. For example, the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics. In one embodiment, the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two. Thus, e.g., the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly prefened. Using these functional groups, the probes can be attached using functional groups on the probes. For example, nucleic acids containing amino groups can be attached to surfaces comprising amino groups, e.g., using available linkers; e.g., homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200). h addition, in some cases, additional linkers, such as alkyl groups (including substituted and heteroalkyl groups) may be used.
In this embodiment, oligonucleotides are synthesized, and then attached to the surface of the solid support. Either the 5' or 3' terminus may be attached to the solid support, or attachment may be via an internal nucleoside. In another embodiment, the immobilization to the solid support may be very strong, yet non-covalent. For example, biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
Alternatively, the oligonucleotides may be synthesized on the surface. For example, photoactivation techniques utilizing photopolymerization compounds and techniques are used. In one embodiment, the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO 95/35505; US Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the Affymetrix GENECHIP® (DNA microchip anay) technology.
Often, amplification-based assays are performed to measure the expression level of soft tissue sarcoma cancer-associated sequences. These assays are typically performed in conjunction with reverse transcription, h such assays, a soft tissue sarcoma cancer-associated nucleic acid sequence acts as a template in an amplification reaction (e.g., Polymerase Chain Reaction, or PCR). In a quantitative amplification, the amount of amplification product will be proportional to the amount of template in the original sample. Comparison to appropriate controls provides a measure of the amount of soft tissue sarcoma cancer-associated RNA. Methods of quantitative amplification are well known. Detailed protocols for quantitative PCR are provided, e.g., in Innis, et al. (1990) PCR Protocols: A Guide to Methods and Applications Academic Press.
In some embodiments, a TAQMAN® (reagents for nucleic acid amplification) based assay is used to measure expression. TAQMAN® based assays use a fluorogenic oligonucleotide probe that contains a 5' fluorescent dye and a 3' quenching agent. The probe hybridizes to a PCR product, but cannot itself be extended due to a blocking agent at the 3' end. When the PCR product is amplified in subsequent cycles, the 5' nuclease activity of the polymerase, e.g., AMPLITAQ® (enzyme for diagnostic applications), results in the cleavage of the TAQMAN® probe. This cleavage separates the 5' fluorescent dye and the 3' quenching agent, thereby resulting in an increase in fluorescence as a function of amplification (see, e.g., literature provided by Perkin-Elmer). Other suitable amplification methods include, but are not limited to, ligase chain reaction (LCR) (see Wu and Wallace (1989) Genomics 4:560-569, Landegren, et al. (1988) Science 241:1077-1080, and Barringer, et al. (1990) Gene 89:117-122), transcription amplification (Kwoh, et al. (1989) Proc. Nat'l Acad. Sci. USA 86:1173- 1177), self-sustained sequence replication (Guatelli, et al. (1990) Proc. Nat'l Acad. Sci. USA 87:1874-1878), dot PCR, linker adapter PCR, etc.
Expression of soft tissue sarcoma cancer-associated proteins from nucleic acids
In one embodiment, soft tissue sarcoma cancer nucleic acids, e.g., encoding soft tissue sarcoma cancer proteins are used to make a variety of expression vectors to express cancer proteins which can then be used in screening assays, as described below. Expression vectors and recombinant DNA technology are well known (see, e.g., Ausubel, supra, and Fernandez and Hoeffler (eds. 1999) Gene Expression Systems Academic Press) and are used to express proteins. The expression vectors may be either self-replicating extrachromosomal vectors or vectors which integrate into a host genome. Generally, these expression vectors include transcriptional and translational regulatory nucleic acid operably linked to the nucleic acid encoding the soft tissue sarcoma cancer protein. The term "control sequences" refers to DNA sequences used for the expression of an operably linked coding sequence in a particular host organism. Control sequences that are suitable for prokaryotes, e.g., include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is typically accomplished by ligation at convenient restriction sites. If such sites do not exist, synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. Transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the soft tissue sarcoma cancer protein; e.g., transcriptional and translational regulatory nucleic acid sequences from Bacillus are preferably used to express the soft tissue sarcoma cancer protein in Bacillus. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known for a variety of host cells.
In general, transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences. In another embodiment, the regulatory sequences include a promoter and transcriptional start and stop sequences.
Promoter sequences encode either constitutive or inducible promoters. The promoters may be either naturally occurring promoters or hybrid promoters. Hybrid promoters, which combine elements of more than one promoter, are also known, and are useful in the present invention.
An expression vector may comprise additional elements. For example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, e.g., in mammalian or insect cells for expression and in a prokaryotic host for cloning and amplification. Furthermore, for integrating expression vectors, the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct. The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are available. See, e.g., Fernandez and Hoeffler, supra; and Kitamura, et al. (1995) Proc. Nat'l Acad. Sci. USA 92:9146- 9150.
In addition, in another embodiment, the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are available and will vary with the host cell used. The soft tissue sarcoma cancer proteins of the present invention are produced by culturing a host cell transformed with an expression vector containing nucleic acid encoding a cancer protein, under the appropriate conditions to induce or cause expression of the cancer protein. Conditions appropriate for soft tissue sarcoma cancer protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained through routine experimentation or optimization. For example, the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction. In addition, in some embodiments, the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.
Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells. Of particular interest are Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells), THP1 cells (a macrophage cell line), and various other human cells and cell lines. hi one embodiment, the soft tissue sarcoma cancer proteins are expressed in mammalian cells. Mammalian expression systems may be used, and include retroviral and adenoviral systems. One expression vector system is a retroviral vector system such as is generally described in PCT/US97/01019 and PCT/US97/01048. Of particular use as mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the S V40 early promoter, mouse mammary tumor virus LTR promoter, adenovims major late promoter, herpes simplex vims promoter, and the CMV promoter (see, e.g., Fernandez and Hoeffler, supra). Typically, transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence. Examples of transcription terminator and polyadenylation signals include those derived form SV40.
Methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, are available, and will vary with the host cell used. Techniques include dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei. h one embodiment, soft tissue sarcoma cancer proteins are expressed in bacterial systems. Promoters from bacteriophage may also be used. In addition, synthetic promoters and hybrid promoters are also useful; e.g., the tac promoter is a hybrid of the trp and lac promoter sequences. Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable. The expression vector may also include a signal peptide sequence that provides for secretion of the soft tissue sarcoma cancer protein in bacteria. The protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria). The bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin, and tetracycline. Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan, and leucine biosynthetic pathways. These components are assembled into expression vectors. Expression vectors for bacteria include vectors for Bacillus subtilis, E. coli,
Streptococcus cremoris, and Streptococcus lividans, among others (e.g., Fernandez and Hoeffler, supra). The bacterial expression vectors are transformed into bacterial host cells using techniques such as calcium chloride treatment, electroporation, and others. hi one embodiment, soft tissue sarcoma cancer proteins are produced in insect cells using, e.g., expression vectors for the transformation of insect cells, and in particular, baculovims-based expression vectors.
In another embodiment, a soft tissue sarcoma cancer protein is produced in yeast cells. Yeast expression systems include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yanowia lipolytica.
The soft tissue sarcoma cancer protein may also be made as a fusion protein, e.g., for the creation of monoclonal antibodies, if the desired epitope is small, the soft tissue sarcoma cancer protein may be fused to a carrier protein to form an immunogen. Alternatively, the soft tissue sarcoma cancer protein may be made as a fusion protein to increase expression, or for other reasons. For example, when the soft tissue sarcoma cancer protein is a peptide, the nucleic acid encoding the peptide may be linked to another nucleic acid for expression purposes. Fusion with detection epitope tags can be made, e.g., with FLAG, His6, myc, HA, etc.
In one embodiment, the soft tissue sarcoma cancer protein is purified or isolated after expression. Soft tissue sarcoma cancer proteins may be isolated or purified in a variety of ways depending on what other components are present in the sample and the requirements for purified product. Standard purification methods include ammonium sulfate precipitations, electrophoretic, molecular, immunological, and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing. For example, the cancer protein may be purified using a standard anti-cancer protein antibody column. Ulfrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. See, e.g., Walsh (2002) Proteins: Biochemistry and Biotechnology Wiley; Hardin, et al. (eds. 2001) Cloning, Gene Expression and Protein Purification Oxford Univ. Press; Wilson, et al. (eds. 2000) Encyclopedia of Separation Science Academic Press; and Scopes (1993) Protein Purification Springer-Verlag. The degree of purification necessary will vary depending on the use of the cancer protein. In some instances no purification will be necessary.
Once expressed and purified if necessary, the soft tissue sarcoma cancer proteins and nucleic acids are useful in a number of applications. They may be used as immunoselection reagents, as vaccine reagents, as screening agents, etc. In one embodiment, the soft tissue sarcoma cancer nucleic acids, proteins, and antibodies of the invention are labeled. By "labeled" herein is meant that a compound has at least one element, isotope, or chemical compound attached to enable the detection of the compound. In general, labels fall into three classes: a) isotopic labels, which may be radioactive or heavy isotopes; b) immune labels, which may be antibodies, antigens, or epitope tags; and c) colored or fluorescent dyes. The labels may be incoφorated into the cancer nucleic acids, proteins, and antibodies. For example, the label should be capable of producing, either directly or indirectly, a detectable signal. The detectable moiety may be a radioisotope, such as ^H, ^C, 32 , 35g5 or 125i5 a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta-galactosidase, or horseradish peroxidase. Methods are known for conjugating the antibody to the label. See, e.g., Hunter, et al. (1962) Nature 144:945; David, et al. (1974) Biochemistry 13:1014-1021; Pain, et al. (1981) J. Immunol. Meth. 40:219- 230; and Nygren (1982) J. Histochem. and Cytochem. 30:407-412.
Accordingly, the present invention also provides soft tissue sarcoma cancer protein sequences. A cancer protein of the present invention may be identified in several ways. "Protein" in this sense includes proteins, polypeptides, and peptides. Nucleic acid sequences of the invention can be used to generate protein sequences, including cloning the entire gene and verifying its frame and amino acid sequence, or by comparing it to known sequences to search for homology to provide a frame, assuming the soft tissue sarcoma cancer protein has an identifiable motif or homology to some protein in the database being used. Generally, the nucleic acid sequences are input into a program that will search all three frames for homology. This is done in an embodiment using the following NCBI Advanced BLAST parameters. The program is blastx or blastn. The database is nr. The input data is as "Sequence in FASTA format". The organism list is "none". The "expect" is 10; the filter is default. The "descriptions" is 500, the "alignments" is 500, and the "alignment view" is pairwise. The "Query Genetic Codes" is standard (1). The matrix is BLOSUM62; gap existence cost is 11, per residue gap cost is 1 ; and the lambda ratio is .85 default. This results in the generation of a putative protein sequence.
Variants of of soft tissue sarcoma cancer-associated proteins Also included within one embodiment of soft tissue sarcoma cancer proteins are amino acid variants of the naturally occurring sequences, as determined herein.
Preferably, the variants are preferably greater than about 75% homologous to the wild-type sequence, more preferably greater than about 80%, even more preferably greater than about 85%, and most preferably greater than 90%. In some embodiments the homology will be as high as about 93-95 or 98%. As for nucleic acids, homology in this context means sequence similarity or identity, with identity being prefened.
This homology will be determined using standard techniques, as are outlined above for nucleic acid homologies. Soft tissue sarcoma cancer proteins of the present invention may be shorter or longer than the wild type amino acid sequences. Thus, in one embodiment, included within the definition of soft tissue sarcoma cancer proteins are portions or fragments of the wild type sequences herein. In addition, as outlined above, the soft tissue sarcoma cancer nucleic acids of the invention may be used to obtain additional coding regions, and thus additional protein sequence. hi another embodiment, the soft tissue sarcoma cancer proteins are derivative or variant cancer proteins as compared to the wild-type sequence. That is, the derivative cancer peptide will often contain at least one amino acid substitution, deletion, or insertion, with amino acid substitutions being particularly useful at an appropriate position.
Also included within one embodiment of soft tissue sarcoma cancer proteins of the present invention are amino acid sequence variants. These variants typically fall into one or more of three classes: substitutional, insertional, or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the cancer protein, using cassette or PCR mutagenesis or other appropriate techniques, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above. However, variant cancer protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis using established techniques. Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the cancer protein amino acid sequence. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics.
While the site or region for introducing an amino acid sequence variation is predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed cancer variants screened for the optimal combination of desired activity. Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, e.g., Ml 3 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of cancer protein activities. Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1-20 amino acids, although considerably larger insertions maybe tolerated. Deletions range from about 1-20 residues, although in some cases deletions may be much larger. Substitutions, deletions, insertions or a combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. However, larger changes may be tolerated in certain circumstances. When small alterations in the characteristics of the cancer protein are desired, substitutions are generally made in accordance with the amino acid substitution chart described.
The variants typically exhibit essentially the same qualitative biological activity and will elicit the same immune response as a naturally-occurring analog, although variants also are selected to modify the characteristics of cancer proteins as needed. Alternatively, the variant may be designed such that a biological activity of the cancer protein is altered. For example, glycosylation sites may be added, altered, or removed.
Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those provided in the definition of "conservative substitution". For example, substitutions may be made which more significantly affect: the stracture of the polypeptide backbone in the area of the alteration, e.g., the alpha-helical or beta-sheet stracture; the charge or hydrophobicity of the molecule at the target site; or the bulk of the side chain. The substitutions which in general are expected to produce the greatest changes in the polypeptide's properties are those in which (a) a hydrophilic sidechain, e.g., serine or threonine, is substituted for (or by) a hydrophobic sidechain, e.g., leucine, isoleucine, phenylalanine, valine, or alanine; (b) a cysteine or proline is substituted for (or by) another residue; (c) a residue having an electropositive side chain, e.g., lysine, arginine, or histidine, is substituted for (or by) an electronegative side chain, e.g., glutamic or aspartic acid; (d) a residue having a bulky side chain, e.g., phenylalanine, is substituted for (or by) one not having a side chain, e.g., glycine; or (e) a proline residue is incoφorated or substituted, which changes the degree of rotational freedom of the peptidyl bond.
The variants typically exhibit a similar qualitative biological activity and will elicit the same immune response as the naturally-occurring analog, although variants also are selected to modify the characteristics of the soft tissue sarcoma cancer proteins as needed. Alternatively, the variant may be designed such that the biological activity of the cancer protein is altered. For example, glycosylation sites may be altered or removed. Covalent modifications of these cancer polypeptides are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a cancer polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a cancer polypeptide. Derivatization with bifunctional agents is useful, e.g., for crosslinking cancer polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-cancer polypeptide antibodies or screening assays. Commonly used crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2- phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, e.g., esters with 4- azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis- N-maleimido- 1,8 -octane and agents such as methyl-3-[(p- azidophenyl)dithio]propioimidate.
Other modifications include deamidation of glutamine and asparagine residues to the conesponding glutamic and aspartic acid residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of serine, threonine, or tyrosine residues, methylation of the γ-amino groups of lysine, arginine, and histidine side chains (e.g., pp. 79-86, Creighton (1992) Proteins: Stracture and Molecular Properties Freeman), acetylation of the N-terminal amine, and amidation of a C- terminal carboxyl group. Another type of covalent modification of a cancer polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide. "Altering the native glycosylation pattern" is intended for puφoses herein to mean deleting one or more carbohydrate moieties found in native sequence cancer polypeptide, and/or adding one or more glycosylation sites that are not present in the native sequence cancer polypeptide. Glycosylation patterns can be altered in many ways. Different cell types may be used to express cancer-associated sequences to exhibit different glycosylation patterns. Addition of glycosylation sites to soft tissue sarcoma cancer polypeptides may also be accomplished by altering the amino acid sequence thereof. The alteration may be made, e.g., by the addition of, or substitution by, one or more serine or threonine residues to the native sequence cancer polypeptide (for O-linked glycosylation sites). The soft tissue sarcoma cancer amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the cancer polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
Another means of increasing the number of carbohydrate moieties on the soft tissue sarcoma cancer polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. See, e.g., WO 87/05330; and pp. 259-306 in Aplin and Wriston (1981) CRC Crit. Rev. Biochem.
Removal of carbohydrate moieties present on the soft tissue sarcoma cancer polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are applicable. See, e.g., Sojar and Bahl (1987) Arch. Biochem. Biophys. 259:52-57; and Edge, et al. (1981) Anal. Biochem. 118:131-137. Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases. See, e.g., Thotakura, et al. (1987) Meth. Enzymol. 138:350-359.
Another type of covalent modification of soft tissue sarcoma cancer protein comprises linking the cancer polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in US Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192; or 4,179,337.
Soft tissue sarcoma cancer polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising a cancer polypeptide fused to another, heterologous polypeptide or amino acid sequence. In one embodiment, such a chimeric molecule comprises a fusion of a cancer polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino-or carboxyl-terminus of the soft tissue sarcoma cancer polypeptide. The presence of such epitope-tagged forms of a cancer polypeptide can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the soft tissue sarcoma cancer polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. In an alternative embodiment, the chimeric molecule may comprise a fusion of a cancer polypeptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule. Various tag polypeptides and their respective antibodies are available. Examples include poly-histidine (poly-his) or poly-l istidine-glycine (poly-his-gly) tags; HIS6, and metal chelation tags, the flu HA tag polypeptide and its antibody 12CA5 (Field, et al. (1988) Mol. Cell. Biol. 8:2159-2165); the c-myc tag and the 8F9, 3C7, 6E10, G4, B7, and 9E10 antibodies thereto (Evan, et al. (1985) Mol. Cell. Biol. 5:3610-3616); and the Heφes Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky, et al. (1990) Protein Engineering 3:547-553). Other tag polypeptides include the Flag-peptide (Hopp, et al. (1988) BioTechnology 6:1204-1210); the KT3 epitope peptide (Martin, et al. (1992) Science 255:192-194); tubulin epitope peptide (Skinner, et al. (1991) J. Biol. Chem. 266:15163-15166); and the T7 gene 10 protein peptide tag (Lutz-Freyermuth, et al. (1990) Proc. Nat'l Acad. Sci. USA 87:6393- 6397).
Also included with an embodiment of soft tissue sarcoma cancer protein are other soft tissue sarcoma cancer proteins of the functional family, and counteφart cancer proteins from other organisms, which are cloned and expressed as outlined below. Thus, probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related cancer proteins from humans or other organisms. Particularly useful probe and/or PCR primer sequences include unique areas of the soft tissue sarcoma cancer nucleic acid sequence. PCR primers are from about 15-35 nucleotides in length, with from about 20-30 being prefened, and may contain inosine as needed. The conditions for the PCR reaction are well known. See, e.g., Innis, PCR Protocols, supra.
In addition, as is outlined herein, soft tissue sarcoma cancer proteins can be made that are longer than those encoded by the nucleic acids of the Tables, e.g., by the elucidation of extended sequences, the addition of epitope or purification tags, the addition of other fusion sequences, etc.
Soft tissue sarcoma cancer proteins may also be identified as being encoded by soft tissue sarcoma cancer nucleic acids. Thus, soft tissue sarcoma cancer proteins are encoded by nucleic acids that will hybridize to the sequences of the sequence listings, or their complements, as outlined herein.
Antibodies to soft tissue sarcoma cancer-associated proteins In one embodiment, when the soft tissue sarcoma cancer protein is to be used to generate antibodies, e.g., for immunotherapy or immunodiagnosis, the soft tissue sarcoma cancer protein should share at least one epitope or determinant with the full length protein. By "epitope" or "determinant" herein is typically meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC. Thus, in most instances, antibodies made to a smaller, e.g., fragment of, cancer protein will be able to bind to the full-length protein, particularly linear epitopes. In one embodiment, the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross-reactivity. In another embodiment, the epitope is selected from a protein sequence set out in Tables 1 A-l IC. Methods of preparing polyclonal antibodies exist (e.g., Coligan, supra; and
Harlow and Lane, supra). Polyclonal antibodies can be raised in a mammal, e.g., by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include a protein encoded by a nucleic acid of the figures or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, semm albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and MPL- TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected without undue experimentation.
The antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495-497. In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include a polypeptide encoded by a nucleic acid of Tables 1A-1 IC, or fragment thereof, or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (e.g., pp. 59-103 in Goding (1986) Monoclonal Antibodies: Principles and Practice Academic Press). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.
In one embodiment, the antibodies are bispecific antibodies. Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens or that have binding specificities for two epitopes on the same antigen. In one embodiment, one of the binding specificities is for a protein encoded by a nucleic acid Tables 1 A-l IC or a fragment thereof, the other one is for another antigen, and preferably for a cell-surface protein or receptor or receptor subunit, preferably one that is tumor specific. Alternatively, tetramer-type technology may create multivalent reagents.
In one embodiment, the antibodies to soft tissue sarcoma cancer protein are capable of reducing or eliminating a biological function of a soft tissue sarcoma cancer protein, as is described below. That is, the addition of anti-soft tissue sarcoma cancer protein antibodies (either polyclonal or preferably monoclonal) to cancer tissue may reduce or eliminate the neoplastic or malignant cancer activity. Generally, at least about 25% decrease in activity, growth, size or the like may be used, with at least about 50% being particularly useful and about 95-100% decrease being especially useful.
In another embodiment the antibodies to the soft tissue sarcoma cancer proteins are humanized antibodies (e.g., Xenerex Biosciences; Medarex, Inc.; Abgenix, Inc.; Protein Design Labs, Inc.). Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non- human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues form a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by conesponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions conespond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will typically comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones, et al. (1986) Nature 321:522-525; Riechmann, et al. (1988) Nature 332:323-329; and Presta (1992) Cun. Op. Struct. Biol. 2:593-596). Humanization can be essentially performed following the method of Winter and co-workers (Jones, et al. (1986) Nature 321 :522- 525; Riechmann, et al. (1988) Nature 332:323-327; Verhoeyen, et al. (1988) Science 239:1534-1536), by substituting rodent CDRs or CDR sequences for conesponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (US Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by conesponding sequence from a non-human species.
Human-like antibodies can also be produced using phage display libraries (Hoogenboom and Winter (1992) J. Mol. Biol. 227:381-388; Marks, et al. (1991) J. Mol. Biol. 222:581-597) or human monoclonal antibodies (e.g., p. 77, Cole, et al. in Reisfeld and Sell (1985) Monoclonal Antibodies and Cancer Therapy Liss; and
Boemer, et al. (1991) J. Immunol. 147:86-95). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in nearly all respects, including gene reareangement, assembly, and antibody repertoire. This approach is described, e.g., in US Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks, et al. (1992) Bio/Technology 10:779-783; Lonberg, et al. (1994) Nature 368:856-859; Morrison (1994) Nature 368:812-13; Fishwild, et al. (1996) Nature Biotechnology 14:845-851, commented on in Neuberger (1996) Nature Biotechnology 14:826; and Lonberg and Huszar (1995) Intern. Rev. Immunol. 13:65-93. By immunotherapy is meant treatment of soft tissue sarcoma cancer or related disease with an antibody raised against, e.g., proteins. As used herein, immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient). Active immunization is the induction of antibody and/or T-cell responses in a recipient (patient). Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised. The antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen, leading to an immune response. In one embodiment the soft tissue sarcoma cancer proteins against which antibodies are raised are secreted proteins as described above. Without being bound by theory, antibodies used for treatment may bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted cancer protein, e.g., in autocrine signaling. In another embodiment, the soft tissue sarcoma cancer protein to which antibodies are raised is a transmembrane protein. Without being bound by theory, antibodies used for treatment often bind the extracellular domain of the cancer protein and prevent it from binding to other proteins, such as circulating ligands or cell- associated molecules. The antibody may cause down-regulation of the transmembrane cancer protein. The antibody may be a competitive, non-competitive, or uncompetitive inhibitor of protein binding to the extracellular domain of the cancer protein. The antibody may be an antagonist of the cancer protein. Further, the antibody prevents activation of the transmembrane cancer protein. In one aspect, when the antibody prevents the binding of other molecules to the cancer protein, the antibody prevents growth of the cell. The antibody may also be used to target or sensitize the cell to cytotoxic agents, including, but not limited to TNF-α, TNF-β, IL- 1, INF-γ, and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like. In some instances the antibody belongs to a sub-type that activates serum complement, or a similar effector function, when complexed with the transmembrane protein thereby mediating cytotoxicity or antigen-dependent cytotoxicity (ADCC). Thus, soft tissue sarcoma cancer is treated by administering to a patient antibodies directed against the transmembrane cancer protein. Antibody-labeling may activate a co-toxin, localize a toxin payload, or otherwise provide means to locally ablate cells.
In another embodiment, the antibody is conjugated or fused to an effector moiety. The effector moiety can be a labeling moiety, e.g., a radioactive or fluorescent label, or a therapeutic moiety. In one aspect the therapeutic moiety is a small molecule that modulates the activity of the soft tissue sarcoma cancer protein. hi another aspect the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the soft tissue sarcoma cancer protein. The therapeutic moiety may inhibit enzymatic activity such as protease or collagenase activity associated with the cancer, or be an attractant of other cells, such as NK cells. See, e.g., Groh, et al. (2002) Nature 419:734-738. In one embodiment, the therapeutic moiety can also be a cytotoxic agent. In this method, targeting the cytotoxic agent to soft tissue sarcoma cancer tissue or cells, results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with cancer. Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drags or toxins or active fragments of such toxins. Suitable toxins and their conesponding fragments include diphtheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin, and the like. Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against soft tissue sarcoma cancer proteins, or binding of a radionuclide to a chelating agent that has been covalently attached to the antibody. Targeting the therapeutic moiety to transmembrane cancer proteins not only serves to increase the local concentration of therapeutic moiety in the cancer afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety. In another embodiment, the soft tissue sarcoma cancer protein against which the antibodies are raised is an intracellular protein. In this case, the antibody may be conjugated or fused to a protein which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis. In another embodiment, a nucleic acid encoding the antibody is administered to the individual or cell. Moreover, wherein the soft tissue sarcoma cancer protein can be targeted within a cell, e.g., the nucleus, an antibody thereto contains a signal for that target localization, e.g., a nuclear localization signal.
The soft tissue sarcoma cancer antibodies of the invention specifically bind to soft tissue sarcoma cancer proteins. By "specifically bind" herein is meant that the antibodies bind to the protein with a K<j of at least about 0.1 mM, more usually at least about 1 μM, preferably at least about 0.1 μM or better, and most preferably, 0.01 μM or better. Selectivity of binding to the specific target and not to related sequences is often also important
Detection of soft tissue sarcoma cancer-associated sequence for diagnostic and therapeutic applications
In one aspect, the RNA expression levels of genes are determined for different cellular states in the soft tissue sarcoma cancer phenotype. Expression levels of genes in normal tissue (e.g., not exhibiting soft tissue sarcoma cancer) and in soft tissue sarcoma cancer tissue (and in some cases, for varying severities of soft tissue sarcoma cancer that relate to prognosis, as outlined below) are evaluated to provide expression profiles. An expression profile of a particular cell state or point of development is essentially a "fingeφrint" of the state. While two states may have a particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is reflective of the state of the cell. By comparing expression profiles of cells in different states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained. Then, diagnosis may be performed or confirmed to determine whether a tissue sample has the gene expression profile of normal or cancer tissue. This will provide for molecular diagnosis of related conditions.
"Differential expression," or grammatical equivalents as used herein, refers to qualitative or quantitative differences in the temporal and/or cellular gene expression patterns within and among cells and tissue. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, e.g., normal versus cancer tissue. Genes may be turned on or turned off in a particular state, relative to another state thus permitting comparison of two or more states. A qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques. Some genes will be expressed in one state or cell type, but not in both. Alternatively, the difference in expression may be quantitative, e.g., in that expression is increased or decreased; e.g., gene expression is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques, e.g., as by use of Affymetrix GENECHIP® expression anays. See, Lockhart (1996) Nature Biotechnology 14:1675-1680. Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, Northern analysis and RNase protection. As outlined above, preferably the change in expression (e.g., upregulation or downregulation) is at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably at least about 200%, with from 300 to at least 1000% being especially useful.
Evaluation may be at the gene transcript, or the protein level. The amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, e.g., with antibodies to the soft tissue sarcoma cancer protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc. Proteins conesponding to soft tissue sarcoma cancer genes, e.g., those identified as being important in a soft tissue sarcoma cancer phenotype, can be evaluated in a soft tissue sarcoma cancer diagnostic test. In one embodiment, gene expression monitoring is performed simultaneously on a number of genes. Multiple protein expression monitoring can be performed as well. Similarly, these assays may be performed on an individual basis as well.
In this embodiment, the soft tissue sarcoma cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of soft tissue sarcoma cancer sequences in a particular cell. The assays are further described below in the example. PCR techniques can be used to provide greater sensitivity. In one embodiment nucleic acids encoding the soft tissue sarcoma cancer protein are detected. Although DNA or RNA encoding the soft tissue sarcoma cancer protein may be detected, of particular interest are methods wherein an mRNA encoding a cancer protein is detected. Probes to detect mRNA can be a nucleotide/deoxynucleotide probe that is complementary to and hybridizes with the mRNA and includes, but is not limited to, oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein. In one method the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample. Following washing to remove the non-specifically bound probe, the label is detected. In another method detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA. Following washing to remove the non-specifically bound probe, the label is detected. For example, a digoxygenin labeled riboprobe (RNA probe) that is complementary to the mRNA encoding a cancer protein is detected by binding the digoxygenin with an anti- digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5- bromo-4-chloro-3-indoyl phosphate.
In one embodiment, various proteins from the three classes of proteins as described herein (secreted, transmembrane or intracellular proteins) are used in diagnostic assays. The soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing cancer sequences are used in diagnostic assays. This can be performed on an individual gene or conesponding polypeptide level. In another embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes and/or conesponding polypeptides.
As described and defined herein, soft tissue sarcoma cancer proteins, including intracellular, transmembrane, or secreted proteins, find use as markers of soft tissue sarcoma cancer, e.g., for prognostic or diagnostic puφoses. Detection of these proteins in putative soft tissue sarcoma cancer tissue allows for detection, prognosis, or diagnosis of cancer, and for selection of therapeutic strategy. In one embodiment, antibodies are used to detect soft tissue sarcoma cancer proteins. One method separates proteins from a sample by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be another type of gel, including isoelectric focusing gels and the like). Following separation of proteins, the cancer protein is detected, e.g., by immunoblotting with antibodies raised against the cancer protein. In another method, antibodies to the soft tissue sarcoma cancer protein find use in in situ imaging techniques, e.g., in histology. See, e.g., Asai, et al. (eds. 1993) Methods in Cell Biology: Antibodies in Cell Biology (vol. 37) Academic Press. In this method cells are contacted with from one to many antibodies to the soft tissue sarcoma cancer protein(s). Following washing to remove non-specific antibody binding, the presence of the antibody or antibodies is detected. In one embodiment the antibody is detected by incubating with a secondary antibody that contains a detectable label. In another method the primary antibody to the soft tissue sarcoma cancer protein(s) contains a detectable label, e.g., an enzyme marker that can act on a substrate. In another embodiment each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of soft tissue sarcoma cancer proteins. Many other histological imaging techniques are also provided by the invention. h one embodiment the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths. In addition, a fluorescence activated cell sorter (FACS) can be used in the method.
In another embodiment, antibodies find use in diagnosing soft tissue sarcoma cancer from biological samples, such as blood, urine, sputum, semen, or other bodily fluids. As previously described, certain cancer proteins are secreted/circulating molecules. Blood or semen samples, therefore, are useful as samples to be probed or tested for the presence of secreted cancer proteins. Antibodies can be used to detect a soft tissue sarcoma cancer protein by previously described immunoassay techniques including ELISA, immunoblotting (Western blotting), immunoprecipitation, BIACORE technology and the like. Conversely, the presence of antibodies may indicate an immune response against an endogenous soft tissue sarcoma cancer protein.
In one embodiment, in situ hybridization of labeled cancer nucleic acid probes to tissue anays is done. For example, anays of tissue samples, including cancer tissue and/or normal tissue, are made. In situ hybridization (see, e.g., Ausubel, supra) is then performed. When comparing the fingeφrints between an individual and a standard, the skilled artisan can make a diagnosis, a prognosis, or a prediction based on the findings. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis and molecular profiling of the condition of the cells may lead to distinctions between responsive or refractory conditions or may be predictive of outcomes.
Assays for Prognosis of Soft Tissue Sarcoma Disorders
In one embodiment, the cancer proteins, antibodies, nucleic acids, modified proteins and cells containing cancer sequences are used in prognosis assays. As above, gene expression profiles can be generated that conelate to soft tissue sarcoma cancer severity, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes included. For example, P-glycoprotein and Ki-67 antigen are promising markers for 5-year overall and disease-free survival for soft tissue sarcoma patients. Levine E.A. et al., Evaluation of new prognostic markers for adult soft tissue sarcomas, J. Clin. Oncol. 15:3249-57 (1997). Other markers may be similarly identified that conelate to soft tissue sarcoma cancer severity, or survival rates of soft tissue sarcoma patients.
As above, cancer probes may be attached to biochips for the detection and quantification of cancer sequences in a tissue or patient. The assays proceed as outlined above for diagnosis. PCR method may provide more sensitive and accurate quantification.
Genes useful in prognostic assays are genes that are differentially expressed according to the stage of illness of the patient. In one embodiment, the genes may be uniquely expressed according to the stage of the patient, h another embodiment, the genes may be expressed at differential levels according to the stage of the patient.
INSERT EXAMPLE OF PROGNOSTIC ASSAY The conelation of genes expressed in the different stages, either uniquely expressed or have differential expression levels according to the stage, may be used to determine the viability of inducing remission in a patient. In addition, genes that are expressed indicating onset of long-term complications may also be useful as a prognostic tool. Assays for therapeutic compounds
The soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing soft tissue sarcoma cancer sequences are used in drag screening assays or by evaluating the effect of drag candidates on a "gene expression profile" or expression profile of polypeptides. In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow momtoring for expression profile genes after treatment with a candidate agent. See, e.g., Zlokarnik, et al. (1998) Science 279:84-88; and Heid (1996) Genome Res. 6:986-994. In one embodiment, the soft tissue sarcoma cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified soft tissue sarcoma cancer proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the soft tissue sarcoma cancer phenotype or an identified physiological function of a soft tissue sarcoma cancer protein. As above, this can be done on an individual gene level or by evaluating the effect of drag candidates on a "gene expression profile". In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow momtoring for expression profile genes after treatment with a candidate agent, see Zlokamik, supra. Having identified the differentially expressed genes herein, a variety of assays may be executed. In one embodiment, assays may be run on an individual gene or protein level. That is, having identified a particular gene as up regulated in soft tissue sarcoma cancer, test compounds can be screened for the ability to modulate gene expression or for binding to the cancer protein. "Modulation" thus includes both an increase and a decrease in gene expression. The amount of modulation will depend on the original change of the gene expression in normal versus tissue exhibiting soft tissue sarcoma cancer, with changes of at least about 10%), preferably about 50%, more preferably about 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4-fold increase in cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in cancer tissue compared to noπnal tissue often provides a target value of a 10-fold increase in expression to be induced by the test compound.
The amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, e.g., through the use of antibodies to the cancer protein and standard immunoassays. Proteomics and separation techniques may also allow quantification of expression.
In one embodiment, gene expression or protein monitoring of a number of entities, e.g., an expression profile, is monitored simultaneously. Such profiles will typically involve a plurality of those entities described herein.
In this embodiment, the soft tissue sarcoma cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of cancer sequences in a particular cell. Alternatively, PCR may be used. Thus, a series, e.g., of microtiter plate, may be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.
Modulators of soft tissue sarcoma cancer
Expression monitoring can be performed to identify compounds that modify the expression of one or more soft tissue sarcoma cancer-associated sequences, e.g., a polynucleotide sequence set out in the Tables. Generally, in one embodiment, a test modulator is added to the cells prior to analysis. Moreover, screens are also provided to identify agents that modulate soft tissue sarcoma cancer, modulate soft tissue sarcoma cancer proteins, bind to a soft tissue sarcoma cancer protein, or interfere with the binding of a soft tissue sarcoma cancer protein and an antibody or other binding partner:
The term "test compound" or "drag candidate" or "modulator" or grammatical equivalents as used herein describes a molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the cancer phenotype or the expression of a cancer sequence, e.g., a nucleic acid or protein sequence, h several embodiments, modulators alter expression profiles, or expression profile nucleic acids or proteins provided herein. In one embodiment, the modulator suppresses a soft tissue sarcoma cancer phenotype, e.g., to a normal tissue fingeφrint. In another embodiment, a modulator induced a cancer phenotype. Generally, a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, e.g., at zero concentration or below the level of detection. Dmg candidates encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 daltons. Small molecules may be less than 2000, or less than 1500, or less than 1000, or less than 500 D. Candidate agents comprise functional groups necessary for stractural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, stractural analogs, or combinations thereof. Particularly useful are peptides.
In one aspect, a modulator will neutralize the effect of a soft tissue sarcoma cancer protein. By "neutralize" is meant that activity of a protein is inhibited or blocked and thereby has substantially no effect on a cell.
In certain embodiments, combinatorial libraries of potential modulators will be screened for an ability to bind to a soft tissue sarcoma cancer polypeptide or to modulate activity. Conventionally, new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound") with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis. See, e.g., Janzen (2002) High Throughput Screening: Methods and Protocols Humana; Devlin (ed. 1997) High Throughput Screening: The Discovery of Bioactive Substances Dekker; and Mei and Czamik (eds. 2002) Integrated Drag Discovery Techniques Dekker.
In one embodiment, high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such "combinatorial chemical libraries" are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds" or can themselves be used as potential or actual therapeutics. A combinatorial chemical library is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks" such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide (e.g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (e.g., the number of amino acids in a polypeptide compound). Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks. See Gallop, et al. (1994) J. Med. Chem. 37:1233-1251. Preparation and screening of combinatorial chemical libraries is well known.
Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., US Patent No. 5,010,175, Furka (1991) Pept. Prot. Res. 37:487-493, Houghton, et al. (1991) Nature 354:84-88), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091), benzodiazepines (US Pat. No. 5,288,514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs, et al. (1993) Proc. Nat'l Acad. Sci. USA 90:6909-6913), vinylogous polypeptides (Hagihara, et al. (1992) J. Amer. Chem. Soc. 114:6568), nonpeptidal peptidomimetics with a Beta-D- Glucose scaffolding (Hirschmann, et al. (1992) J. Amer. Chem. Soc. 114:9217-9218), analogous organic syntheses of small compound libraries (Chen, et al. (1994) J. Amer. Chem. Soc. 116:2661), oligocarbamates (Cho, et al. (1993) Science 261:1303-1305), and/or peptidyl phosphonates (Campbell, et al. (1994) J. Org. Chem. 59:658-xxx). See, generally, Gordon, et al. (1994) J. Med. Chem. 37:1385-1401, nucleic acid libraries (see, e.g., Stratagene, Coφ.), peptide nucleic acid libraries (see, e.g., US Patent 5,539,083), antibody libraries (see, e.g., Vaughn, et al. (1996) Nature
Biotechnology 14:309-314, and PCT/US96/10287), carbohydrate libraries (see, e.g.,< Liang, et al. (1996) Science 274:1520-1522, and US Patent No. 5,593,853), and small organic molecule libraries (see, e.g., benzodiazepines, page 33 Baum (Jan 18, 1993) C&E News); isoprenoids (US Patent No. 5,569,588); thiazolidinones and metathiazanones (US Patent No. 5,549,974); pynolidines (US Patent Nos. 5,525,735 and 5,519,134); moφholino compounds (US Patent No. 5,506,337); benzodiazepines (US Patent No. 5,288,514); and the like.
Devices for the preparation of combinatorial libraries are commercially available. See, e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville KY; Symphony, Rainin, Woburn, MA; 433A Applied Biosystems, Foster City, CA; 9050 Plus, Milhpore, Bedford, MA.
A number of well known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations like the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Coφoration, Hopkinton, MA; Orca, Hewlett-Packard, Palo Alto, CA), which mimic the manual synthetic operations performed by a chemist. The above devices are suitable for use with the present invention. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent. In addition, numerous combinatorial libraries are themselves commercially available. See, e.g., ComGenex, Princeton, NJ; Asinex, Moscow, Ru; Tripos, Inc., St. Louis, MO; ChemStar, Ltd, Moscow, RU; 3D Pharmaceuticals, Exton, PA; Martek Biosciences, Columbia, MD; etc. The assays to identify modulators are amenable to high throughput screening.
Assays thus detect enhancement or inhibition of cancer gene transcription, inhibition or enhancement of polypeptide expression, and inhibition or enhancement of polypeptide activity.
High throughput assays for the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known, as are binding assays and reporter gene assays. Thus, e.g., US Patent No. 5,559,410 discloses high throughput screening methods for proteins, US Patent No. 5,585,639 discloses high throughput screening methods for nucleic acid binding (e.g., in anays), while US Patent Nos. 5,576,220 and 5,541,061 disclose high throughput methods of screening for ligand/antibody binding.
In addition, high throughput screening systems are commercially available. See, e.g., Zymark Coφ., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc., Fullerton, CA; Precision Systems, Inc., Natick, MA, etc. These systems typically automate entire procedures, including sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e.g., Zymark Coφ. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.
In one embodiment, modulators are proteins, often naturally occurring proteins or fragments of naturally occurring proteins. Thus, e.g., cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, may be used. In this way libraries of proteins may be made for screening in the methods of the invention. Particularly useful in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, including human proteins. Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes or ligands and receptors.
In one embodiment, modulators are peptides of from about 5-30 amino acids, with from about 5-20 amino acids being prefened, and from about 7-15 being particularly prefened. The peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides. By "randomized" or grammatical equivalents herein is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. Since generally these random peptides (or nucleic acids, discussed below) are chemically synthesized, they may incoφorate nucleotide or amino acid variations. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.
In one embodiment, the library is fully randomized, with no sequence preferences or constants. In one embodiment, the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities. For example, in one embodiment, the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines, or histidines for phosphorylation sites, etc., or to purines, etc.
Modulators of soft tissue sarcoma cancer can also be nucleic acids, as defined above.
As described above generally for proteins, nucleic acid modulating agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. For example, digests of prokaryotic or eukaryotic genomes maybe used as is outlined above for proteins. hi one embodiment, the candidate compounds are organic chemical moieties, a wide variety of which are available in the literature. After the candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing a target sequence to be analyzed is added to the biochip. If required, the target sequence is prepared using known techniques. For example, the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate. For example, an in vitro transcription with labels covalently attached to the nucleotides is performed. Generally, the nucleic acids are labeled with biotin- FITC or PE, or with cy3 or cy5. h one embodiment, the target sequence is labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected. Alternatively, the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.
These assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes. See, e.g., US Patent Nos. 5,681,702; 5,597,909; 5,545,730; 5,594,117; 5,591,584; 5,571,670; 5,580,731; 5,571,670; 5,591,584; 5,624,802; 5,635,352; 5,594,118; 5,359,100; 5,124,246; and 5,681,697. The target nucleic acid may be prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
A variety of hybridization conditions may be used in the present invention, including high, moderate, and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allows formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration, pH, organic solvent concentration, etc.
These parameters may also be used to control non-specific binding. See US Patent No. 5,681,697. Thus it may be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.
The reactions outlined herein may be accomplished in a variety of ways. Components of the reaction may be added simultaneously, or sequentially, in different orders, with several embodiments outlined below. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g., albumin, detergents, etc., which may be used to facilitate optimal hybridization and detection, and/or reduce non-specific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target.
The assay data are analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.
Screens are performed to identify modulators of the soft tissue sarcoma cancer phenotype. In one embodiment, screening is performed to identify modulators that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype. hi another embodiment, e.g., for diagnostic applications, having identified differentially expressed genes important in a particular state, screens can be performed to identify modulators that alter expression of individual genes. In an another embodiment, screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product. In addition, screens can be done for genes that are induced in response to a candidate agent. After identifying a modulator based upon its ability to suppress a soft tissue sarcoma cancer expression pattern leading to a normal expression pattern, or to modulate a single cancer gene expression profile so as to mimic the expression of the gene from normal tissue, a screen as described above can be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated soft tissue sarcoma cancer tissue reveals genes that are not expressed in normal tissue or soft tissue sarcoma cancer tissue, but are expressed in agent treated tissue. These agent-specific sequences can be identified and used by methods described herein for cancer genes or proteins. In particular, these sequences and the proteins they encode find use in marking or identifying agent treated cells. In addition, antibodies can be raised against the agent induced proteins and used to target novel therapeutics to the treated soft tissue sarcoma cancer tissue sample. Thus, in one embodiment, a test compound is administered to a population of cancer cells, that have an associated soft tissue sarcoma cancer expression profile. By "administration" or "contacting" herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface. In some embodiments, nucleic acid encoding a proteinaceous candidate agent (e.g., a peptide) may be put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is achieved. See PCT US97/01019. Regulatable gene therapy systems can also be used.
Once the test compound has been administered to the cells, the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
Thus, e.g., soft tissue sarcoma cancer tissue may be screened for agents that modulate, e.g., induce or suppress the cancer phenotype. A change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on the cancer activity. By defining such a signature for the soft tissue sarcoma cancer phenotype, screens for new drugs that alter the phenotype can be devised. With this approach, the drug target need not be known and need not be represented in the original expression screening platform, nor does the level of transcript for the target protein need to change.
In one embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself can be done. The gene products of differentially expressed genes are sometimes refened to herein as "cancer proteins" or a "cancer modulatory protein". The cancer modulatory protein may be a fragment, or alternatively, be the full length protein to the fragment encoded by the nucleic acids of the Tables. Preferably, the cancer modulatory protein is a fragment. In one embodiment, the cancer amino acid sequence which is used to determine sequence identity or similarity is encoded by a nucleic acid of the Tables, hi another embodiment, the sequences are naturally occurring allelic variants of a protein encoded by a nucleic acid of the Tables. In another embodiment, the sequences are sequence variants as further described herein. Preferably, the cancer modulatory protein is a fragment of approximately 14-
24 amino acids long. More preferably the fragment is a soluble fragment. Preferably, the fragment includes a non-transmembrane region. In one embodiment, the fragment has an N-terminal Cys to aid in solubility. In one embodiment, the C-terminus of the fragment is kept as a free acid and the N-terminus is a free amine to aid in coupling, e.g., to cysteine.
In one embodiment the cancer proteins are conjugated to an immunogenic agent as discussed herein, h one embodiment the cancer protein is conjugated to BSA
Measurements of soft tissue sarcoma cancer polypeptide activity, or of soft tissue sarcoma cancer or cancer phenotype can be performed using a variety of assays. For example, the effects of the test compounds upon the function of the soft tissue sarcoma cancer polypeptides can be measured by examining parameters described above. A suitable physiological change that affects activity can be used to assess the influence of a test compound on the polypeptides of this invention. When the functional consequences are determined using intact cells or animals, one can also measure a variety of effects associated with tumors, tumor growth, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e.g., northern blots), changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as cGMP. In the assays of the invention, mammalian soft tissue sarcoma cancer polypeptide is typically used, e.g., mouse, preferably human.
Assays to identify compounds with modulating activity can be performed in vitro. For example, a soft tissue sarcoma cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from about 0.5- 48 hours. In one embodiment, the soft tissue sarcoma cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA. The level of protein is typically measured using immunoassays such as western blotting, ELISA, and the like with an antibody that selectively binds to the soft tissue sarcoma cancer polypeptide or a fragment thereof. For measurement of mRNA, amplification, e.g., using PCR, LCR, or hybridization assays, e.g., northern hybridization, RNAse protection, dot blotting, are included. The level of protein or mRNA is typically detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.
Alternatively, a reporter gene system can be devised using a soft tissue sarcoma cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or β-gal. The reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques.
In one embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself can be done. The gene products of differentially expressed genes are sometimes refened to herein as "soft tissue sarcoma cancer proteins." The soft tissue sarcoma cancer protein may be a fragment, or alternatively, the full length protein to a fragment shown herein. hi one embodiment, screening for modulators of expression of specific genes is performed. Typically, the expression of only one or a few genes are evaluated. In another embodiment, screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate stracture activity relationships.
In another embodiment, binding assays are done. In general, purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made. For example, antibodies are generated to the protein gene products, and standard immunoassays are run to determine the amount of protein present. Alternatively, cells comprising the soft tissue sarcoma cancer proteins can be used in the assays.
Thus, in one embodiment, the methods comprise combining a soft tissue sarcoma cancer protein and a candidate compound, and determining the binding of the compound to the soft tissue sarcoma cancer protein. Other embodiments utilize the human soft tissue sarcoma cancer protein, although other mammalian proteins may also be used, e.g., for the development of animal models of human disease. In some embodiments, as outlined herein, variant or derivative soft tissue sarcoma cancer proteins may be used. Generally, in one embodiment of the methods herein, the soft tissue sarcoma cancer protein or the candidate agent is non-diffusibly bound to an insoluble support, preferably having isolated sample receiving areas (e.g., a microtiter plate, an array, etc.). The insoluble supports may be made of a composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports may be solid or porous and of a convenient shape. Examples of suitable insoluble supports include microtiter plates, anays, membranes and beads. These are typically made of glass, plastic (e.g., polystyrene), polysaccharides, nylon, or nitrocellulose, TEFLON® (synthetic resinous flurorine-containing polymers), etc. Microtiter plates and anays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition is typically compatible with the reagents and overall methods of the invention, maintains the activity of the composition, and is nondiffusable. Other methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protein is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine semm albumin (BSA), casein, or other innocuous protein or other moiety. In one embodiment, the soft tissue sarcoma cancer protein is bound to the support, and a test compound is added to the assay. Alternatively, the candidate agent is bound to the support and the cancer protein is added. Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.), and the like.
The determination of the binding of the test modulating compound to the cancer protein may be done in many ways, hi one embodiment, the compound is labeled, and binding determined directly, e.g., by attaching all or a portion of the cancer protein to a solid support, adding a labeled candidate agent (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps may be utilized as appropriate. h some embodiments, only one of the components is labeled, e.g., the proteins (or proteinaceous candidate compounds) can be labeled. Alternatively, more than one component can be labeled with different labels, e.g., 125I for the proteins and a fluorophor for the compound. Proximity reagents, e.g., quenching or energy transfer reagents are also useful.
In one embodiment, the binding of the test compound is determined by competitive binding assay. The competitor may be a binding moiety known to bind to the target molecule (e.g., a soft tissue sarcoma cancer protein), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding between the compound and the binding moiety, with the binding moiety displacing the compound. In one embodiment, the test compound is labeled. Either the compound, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at a temperature which facilitates optimal activity, typically between about 4-40° C. Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening. Typically between about 0.1-1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
In one embodiment, the competitor is added first, followed by a test compound. Displacement of the competitor is an indication that the test compound is binding to the cancer protein and thus is capable of binding to, and potentially modulating, the activity of the cancer protein. In this embodiment, either component can be labeled. Thus, e.g., if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent. Alternatively, if the test compound is labeled, the presence of the label on the support indicates displacement. In an alternative embodiment, the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate that the test compound is bound to the cancer protein with a higher affinity. Thus, if the test compound is labeled, the presence of the label on the support, coupled with a lack of competitor binding, may indicate that the test compound is capable of binding to the cancer protein.
In one embodiment, the methods comprise differential screening to identity agents that are capable of modulating the activity of the cancer proteins, hi one embodiment, the methods comprise combining a cancer protein and a competitor in a first sample. A second sample comprises a test compound, a cancer protein, and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the cancer protein. Alternatively, differential screening is used to identify drag candidates that bind to the native soft tissue sarcoma cancer protein, but cannot bind to modified soft tissue sarcoma cancer proteins. The stracture of the cancer protein may be modeled, and used in rational dmg design to synthesize agents that interact with that site. Drag candidates that affect the activity of the cancer protein are also identified by screening drags for the ability to either enhance or reduce the activity of the protein.
Positive controls and negative controls may be used in the assays. Preferably control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, samples are washed free of non- specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
A variety of other reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g., albumin, detergents, etc., which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in an order that provides for the requisite binding.
In one embodiment, the invention provides methods for screening for a compound capable of modulating the activity of a cancer protein. The methods comprise adding a test compound, as defined above, to a cell comprising cancer proteins. Useful cell types include almost any cell. The cells contain a recombinant nucleic acid that encodes a cancer protein. In one embodiment, a library of candidate agents are tested on a plurality of cells.
In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (e.g., cell-cell contacts). In another example, the determinations are determined at different stages of the cell cycle process.
In this way, compounds that modulate soft tissue sarcoma cancer agents are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the cancer protein. Once identified, similar structures are evaluated to identify critical stractural feature of the compound.
In one embodiment, a method of inhibiting soft tissue sarcoma cancer cell division is provided. The method comprises administration of a soft tissue sarcoma cancer inhibitor. In another embodiment, a method of inhibiting soft tissue sarcoma cancer is provided. The method may comprise administration of a soft tissue sarcoma cancer inhibitor, hi a further embodiment, methods of treating cells or individuals with soft tissue sarcoma cancer are provided, e.g., comprising administration of a soft tissue sarcoma cancer inhibitor.
In one embodiment, a soft tissue sarcoma cancer inhibitor is an antibody as discussed above. In another embodiment, the soft tissue sarcoma cancer inhibitor is an antisense molecule.
A variety of cell growth, proliferation, viability, and metastasis assays are known, as described below. Soft agar growth or colony formation in suspension
Normal cells require a solid substrate to attach and grow. When the cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in stined suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, regenerate normal phenotype and require a solid substrate to attach and grow. Soft agar growth or colony formation in suspension assays can be used to identify modulators of soft tissue sarcoma cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A therapeutic compound would reduce or eliminate the host cells' ability to grow in stined suspension culture or suspended in semi-solid media, such as semi-solid or soft.
Techniques for soft agar growth or colony formation in suspension assays are described, e.g., in Freshney (1998) Culture of Animal Cells: A Manual of Basic Technique (3d ed.) Wiley-Liss; Freshney (2000) Culture of Animal Cells: A Manual of Basic Technique (4th ed.) Wiley-Liss; and Garkavtsev, et al. (1996) Nature Genet. 14:415-20.
Contact inhibition and density limitation of growth Normal cells typically grow in a flat and organized pattern in a petri dish until they touch other cells. When the cells touch one another, they are contact inhibited and stop growing. When cells are transformed, however, the cells are not contact inhibited and continue to grow to high densities in disorganized foci. Thus, the transformed cells grow to a higher saturation density than normal cells. This can be detected moφhologically by the formation of a disoriented monolayer of cells or rounded cells in foci within the regular pattern of normal sunounding cells.
Alternatively, labeling index with (3H)-thymidine at saturation density can be used to measure density limitation of growth. See Freshney (2000), supra. The transformed cells, when transfected with tumor suppressor genes, regenerate a normal phenotype and become contact inhibited and would grow to a lower density.
In this assay, labeling index with (3H)-thymidine at saturation density is a method of measuring density limitation of growth. Transformed host cells are transfected with a soft tissue sarcoma cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions. The percentage of cells labeling with (3H)-thymidine is determined autoradiographically. See, Freshney (1998), supra.
Growth factor or serum dependence
Transformed cells typically have a lower serum dependence than their normal counteφarts. See, e.g., Temin (1966) J. Nat'l Cancer Inst. 37:167-175; Eagle, et al. (1970) J. Exp. Med. 131:836-879; Freshney, supra. This is in part due to release of various growth factors by the transformed cells. Growth factor or serum dependence of transformed host cells can be compared with that of control.
Tumor specific markers levels
Tumor cells release an increased amount of certain factors (hereinafter "tumor specific markers") than their normal counteφarts. For example, plasminogen activator (PA) is released from human glioma at a higher level than from normal brain cells. See, e.g., Gullino "Angiogenesis, tumor vascularization, and potential interference with tumor growth" pp. 178-184 in Mihich (ed. 1985) Biological Responses in Cancer Plenum. Similarly, tumor angiogenesis factor (TAF) is released at a higher level in tumor cells than their normal counteφarts. See, e.g., Folkman (1992) "Angiogenesis and Cancer" Sem Cancer Biol. 3:89-96.
Various techniques which measure the release of these factors are described in Freshney (1994), supra. See also, Unkeless, et al. (1974) J. Biol. Chem. 249:4295- 4305; Strickland and Beers (1976) J. Biol. Chem. 251:5694-5702; Whur, et al. (1980) Br. J. Cancer 42:305-312; Gullino, "Angiogenesis, tumor vascularization, and potential interference with tumor growth" pp. 178-184 in Mihich (ed. 1985)
Biological Responses in Cancer Plenum; Freshney (1985) Anticancer Res. 5:111-130.
Invasiveness into Matrigel
The degree of invasiveness into Matrigel or some other extracellular matrix constituent can be used as an assay to identify compounds that modulate soft tissue sarcoma cancer-associated sequences. Tumor cells exhibit a good conelation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent. In this assay, tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells.
Techniques described in Freshney (1994), supra, can be used. Briefly, the level of invasion of host cells can be measured by using filters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 125I and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra.
Tumor growth in vivo
Effects of soft tissue sarcoma cancer-associated sequences on cell growth can be tested in transgenic or immune-suppressed mice. Knock-out transgenic mice can be made, in which the cancer gene is dismpted or in which a cancer gene is inserted. Knock-out transgenic mice can be made by insertion of a marker gene or other heterologous gene into the endogenous cancer gene site in the mouse genome via homologous recombination. Such mice can also be made by substituting the endogenous cancer gene with a mutated version of the cancer gene, or by mutating the endogenous cancer gene, e.g., by exposure to carcinogens. A DNA construct is introduced into the nuclei of embryonic stem cells. Cells containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re-implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells partially derived from the mutant cell line. Therefore, by breeding the chimeric mice it is possible to obtain a new line of mice containing the introduced genetic lesion. See, e.g., Capecchi, et al. (1989) Science 244:1288-1292. Chimeric targeted mice can be derived according to Hogan, et al. (1988) Manipulating the Mouse Embryo: A Laboratory Manual CSH Press; and Robertson (ed. 1987) Teratocarcinomas and Embryonic Stem Cells: A Practical Approach IRL Press, Washington, D.C. Alternatively, various immune-suppressed or immune-deficient host animals can be used. For example, genetically athymic "nude" mouse (see, e.g., Giovanella, et al. (1974) J. Natl. Cancer hist. 52:921-930), a SCID mouse, a thymectomized mouse, or an inadiated mouse (see, e.g., Bradley, et al. (1978) Br. J. Cancer 38:263-272; Selby, et al. (1980) Br. J. Cancer 41 :52-61) can be used as a host. Transplantable tumor cells (typically about 10°" cells) injected into iso genie hosts will produce invasive tumors in a high proportions of cases, while normal cells of similar origin will not. In hosts which developed invasive tumors, cells expressing a soft tissue sarcoma cancer-associated sequences are injected subcutaneously. After a suitable length of time, preferably about 4-8 weeks, tumor growth is measured (e.g., by volume or by its two largest dimensions) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth.
Polynucleotide modulators of soft tissue sarcoma cancer Antisense and RNAi Polynucleotides
In certain embodiments, the activity of a soft tissue sarcoma cancer-associated protein is downregulated, or entirely inhibited, by the use of antisense polynucleotide, e.g., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a soft tissue sarcoma cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA. h the context of this invention, antisense polynucleotides can comprise naturally-occurring nucleotides, or synthetic species formed from naturally-occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter-sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species. Analogs are comprehended by this invention so long as they function effectively to hybridize with the soft tissue sarcoma cancer protein mRNA. See, e.g., Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA.
Such antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems. The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known. Antisense molecules as used herein include antisense or sense oligonucleotides. Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti-sense strand. The antisense and sense oligonucleotide comprise a single-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for soft tissue sarcoma cancer molecules. An antisense molecule is for a soft tissue sarcoma cancer sequence in Tables 1 A-l IC, or for a ligand or activator thereof. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e.g., Stein and Cohen (1988) Cancer Res. 48:2659-2668; and van der Krol, et al. (1988) BioTechniques 6:958-976. RNA interference is a mechanism to suppress gene expression in a sequence specific manner. See, e.g., Bru elkamp, et al. (2002) Sciencexpress (21March2002); Shaφ (1999) Genes Dev. 13:139-141; and Cathew (2001) Cun. Op. Cell Biol. 13:244-248. In mammalian cells, short, e.g., 21 nt, double stranded small interfering RNAs (siRNA) have been shown to be effective at inducing an RNAi response. See, e.g., Elbashir, et al. (2001) Nature 411 :494-498. The mechanism may be used to downregulate expression levels of identified genes, e.g., treatment of or validation of relevance to disease.
Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of soft tissue sarcoma cancer-associated nucleotide sequences. A ribozyme is an RNA molecule that catalytically cleaves other RNA molecules.
Different kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, haiφin ribozymes, RNase P, and axhead ribozymes. See, e.g., Castanotto, et al. (1994) Adv. in Pharmacology 25:289-317.
General features of haiφin ribozymes are described, e.g., in Hampel, et al.
(1990) Nuc. Acids Res. 18:299-304; European Patent Publication No. 0 360 257; US
Patent No. 5,254,678. Methods of preparation are available. See, e.g., WO 94/26877;
Yu, et al. (1993) Proc. Nat'l Acad. Sci. USA 90:6340-6344; Yamada, et al. (1994) Human Gene Therapy 1 :39-45; Leavitt, et al. (1995) Proc. Nat'l Acad. Sci. USA
92:699-703; Leavitt, et al. (1994) Human Gene Therapy 5:1151-120; and Yamada, et al. (1994) Virology 205: 121-126.
Polynucleotide modulators of soft tissue sarcoma cancer may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its conesponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a polynucleotide modulator of soft tissue sarcoma cancer may be introduced into a cell containing the target nucleic acid sequence, e.g., by formation of an polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.
Thus, in one embodiment, methods of modulating soft tissue sarcoma cancer in cells or organisms are provided. In one embodiment, the methods comprise administering to a cell an anti-soft tissue sarcoma cancer antibody that reduces or eliminates the biological activity of an endogenous soft tissue sarcoma cancer protein. Alternatively, the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a soft tissue sarcoma cancer protein. This may be accomplished in many ways. In one embodiment, e.g., when the soft tissue sarcoma cancer sequence is down-regulated in soft tissue sarcoma cancer, such state may be reversed by increasing the amount of soft tissue sarcoma cancer gene product in the cell. This can be accomplished, e.g., by overexpressing the endogenous soft tissue sarcoma cancer gene or administering a gene encoding the soft tissue sarcoma cancer sequence, using known gene-therapy techniques. In one embodiment, the gene therapy techniques include the incoφoration of the exogenous gene using enhanced homologous recombination (EHR), e.g., as described in PCT/US93/03868, hereby incoφorated by reference in its entirety. Alternatively, e.g., when the soft tissue sarcoma cancer sequence is up-regulated in soft tissue sarcoma cancer, the activity of the endogenous soft tissue sarcoma cancer gene is decreased, e.g., by the administration of a soft tissue sarcoma cancer antisense nucleic acid or other inhibitor, such as RNAi.
In one embodiment, the soft tissue sarcoma cancer proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to soft tissue sarcoma cancer proteins. Similarly, the soft tissue sarcoma cancer proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify cancer antibodies useful for production, diagnostic, or therapeutic purposes. In one embodiment, the antibodies are generated to epitopes unique to a cancer protein; that is, the antibodies show little or no cross- reactivity to other proteins. The soft tissue sarcoma cancer antibodies may be coupled to standard affinity chromatography columns and used to purify cancer proteins. The antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the cancer protein.
Methods of identifying variant soft tissue sarcoma cancer-associated sequences Without being bound by theory, expression of various soft tissue sarcoma cancer sequences is conelated with cancer. Accordingly, disorders based on mutant or variant soft tissue sarcoma cancer genes may be determined. In one embodiment, the invention provides methods for identifying cells containing variant soft tissue sarcoma cancer genes, e.g., determining all or part of the sequence of at least one endogenous soft tissue sarcoma cancer gene in a cell. This may be accomplished using known sequencing techniques. In one embodiment, the invention provides methods of identifying the cancer genotype of an individual, e.g., determining all or part of the sequence of at least one soft tissue sarcoma cancer gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced soft tissue sarcoma cancer gene to a known soft tissue sarcoma cancer gene, e.g., a wild-type gene.
The sequence of all or part of the soft tissue sarcoma cancer gene can then be compared to the sequence of a known soft tissue sarcoma cancer gene to determine if differences exist. This can be done using known homology programs, such as Bestfit, etc. In another embodiment, the presence of a difference in the sequence between the soft tissue sarcoma cancer gene of the patient and the known soft tissue sarcoma cancer gene conelates with a disease state or a propensity for a disease state, as outlined herein. In one embodiment, the soft tissue sarcoma cancer genes are used as probes to determine the number of copies of the soft tissue sarcoma cancer gene in the genome.
In another embodiment, the soft tissue sarcoma cancer genes are used as probes to determine the chromosomal localization of the soft tissue sarcoma cancer genes. Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the soft tissue sarcoma cancer gene locus.
Administration of pharmaceutical and vaccine compositions In one embodiment, a therapeutically effective dose of a soft tissue sarcoma cancer protein or modulator thereof, is administered to a patient. By "therapeutically effective dose" herein is meant a dose that produces effects for which it is administered. The exact dose will depend on the puφose of the treatment, and can be ascertained using known techniques. See, e.g., Ansel, et al. (1999) Pharmaceutical Dosage Forms and Drag Delivery Lippincott; Lieberman (1992) Pharmaceutical Dosage Fomis (vols. 1-3) Dekker, ISBN 0824770846, 082476918X, 0824712692, 0824716981; Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding Amer. Pharmaceut. Assn.; and Pickar (1998) Dosage Calculations Thomson. Adjustments for soft tissue sarcoma cancer degradation, systemic versus localized delivery, and rate of new protease synthesis, as well as the age, body weight, general health, sex, diet, time of administration, drag interaction, and the severity of the condition may be necessary. U.S. Patent Application N. 09/687,576, further discloses the use of compositions and methods of diagnosis and treatment in cancer.
A "patient" for the purposes of the present invention includes both humans and other animals, particularly mammals. Thus the methods are applicable to both human therapy and veterinary applications. In one embodiment the patient is a mammal, preferably a primate, including humans.
The administration of the soft tissue sarcoma cancer proteins and modulators thereof of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, intranasally, transdermally topically, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly. In some instances, e.g., in the treatment of wounds and inflammation, the soft tissue sarcoma cancer proteins and modulators may be directly applied as a solution, spray, or ointment. The pharmaceutical compositions of the present invention comprise a soft tissue sarcoma cancer protein in a form suitable for administration to a patient. In one embodiment, the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts. "Pharmaceutically acceptable acid addition salt" refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyravic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. "Pharmaceutically acceptable base addition salts" include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Particularly useful are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
The phannaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, com and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol. The pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. For example, unit dosage fonns suitable for oral administration include, but are not limited to, powder, tablets, pills, capsules, and lozenges. It is recognized that soft tissue sarcoma cancer protein modulators (e.g., antibodies, antisense constmcts, ribozymes, small organic molecules, etc.) when administered orally, should be protected from digestion. This is typically accomplished either by complexing the molecule(s) with a composition to render it resistant to acidic and enzymatic hydrolysis, or by packaging the molecule(s) in an appropriately resistant carrier, such as a liposome or a protection banier. Means of protecting agents from digestion are available.
The compositions for administration will commonly comprise a soft tissue sarcoma cancer protein modulator dissolved in a pharmaceutically acceptable carrier, preferably an aqueous carrier. A variety of aqueous carriers can be used, e.g., buffered saline and the like. These solutions are sterile and generally free of undesirable matter. These compositions may be sterilized by conventional, well known sterilization techniques. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate, and the like. The concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight, and the like in accordance with the particular mode of administration selected and the patient's needs. See, e.g., (1980) Remington's Pharmaceutical Science (18th ed.) Mack; and Hardman and Limbird (eds. 2001) Goodman and Gilman: The Pharmacological Basis of Therapeutics (10th ed.) McGraw-Hill.
Thus, a typical pharmaceutical composition for intravenous admimstration would be about 0.1 to 10 mg per patient per day. Dosages from about 0.1 to 100 mg per patient per day may be used, particularly when the drag is administered to a secluded site and not into the blood stream, such as into a body cavity or into a lumen of an organ. Substantially higher dosages are possible in topical administration. Actual methods for preparing parenterally administrable compositions will be known or apparent.
The compositions containing modulators of soft tissue sarcoma cancer proteins can be administered for therapeutic or prophylactic treatments, h therapeutic applications, compositions are administered to a patient suffering from a disease (e.g., a cancer) in an amount sufficient to cure or at least partially anest the disease and its complications. An amount adequate to accomplish this is defined as a "therapeutically effective dose." Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health. Single or multiple administrations of the compositions maybe administered depending on the dosage and frequency as required and tolerated by the patient. The composition should provide a sufficient quantity of the agents of this invention to effectively treat the patient. An amount of modulator that is capable of preventing or slowing the development of soft tissue sarcoma cancer in a mammal is refened to as a
"prophylactically effective dose." The particular dose required for a prophylactic treatment will depend upon the medical condition and history of the mammal, the particular stage or form of soft tissue sarcoma cancer disorder being prevented, as well as other factors such as age, weight, gender, administration route, efficiency, etc. Such prophylactic treatments may be used, e.g., in a mammal who has previously had cancer to prevent a recurrence of the cancer, or in a mammal who is suspected of having a significant likelihood of developing cancer, based, at least in part, upon gene expression profiles. Vaccine strategies may be used, in either a DNA vaccine form, or protein vaccine.
It will be appreciated that the present soft tissue sarcoma cancer protein- modulating compounds can be administered alone or in combination with additional soft tissue sarcoma cancer modulating compounds or with other therapeutic agent, e.g., other anti-cancer agents or treatments. In numerous embodiments, one or more nucleic acids, e.g., polynucleotides comprising nucleic acid sequences set forth in Tables 1A-11C, such as RNAi, antisense polynucleotides, or ribozymes, will be introduced into cells, in vitro or in vivo. The present invention provides methods, reagents, vectors, and cells useful for expression of soft tissue sarcoma cancer-associated polypeptides and nucleic acids using in vitro (cell-free), ex vivo, or in vivo (cell or organism-based) recombinant expression systems.
The particular procedure used to introduce the nucleic acids into a host cell for expression of a protein or nucleic acid is application specific. Many procedures for introducing foreign nucleotide sequences into host cells may be used. These include the use of calcium phosphate transfection, spheroplasts, electroporation, liposomes, microinjection, plasma vectors, viral vectors, and other well known methods for introducing cloned genomic DNA, cDNA, synthetic DNA, or other foreign genetic material into a host cell. See, e.g., Berger and Kimmel (1987) Guide to Molecular Cloning Techniques from Methods in Enzymology (vol. 152) Academic Press; Ausubel, et al. (eds. 1999 and supplements) Cunent Protocols Lippincott; and
Sambrook, et al. (2001) Molecular Cloning: A Laboratory Manual (3d ed., Vol. 1-3) CSH Press.
In one embodiment, soft tissue sarcoma cancer proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above. Similarly, cancer genes (including both the full-length sequence, partial sequences, or regulatory sequences of the cancer coding regions) can be administered in a gene therapy application. These cancer genes can include inhibitory applications, e.g., inhibitory RNA, gene therapy (e.g., for incoφoration into the genome), or antisense compositions. Soft tissue sarcoma cancer polypeptides and polynucleotides can also be administered as vaccine compositions to stimulate HTL, CTL, and antibody responses. Such vaccine compositions can include, e.g., lipidated peptides (see, e.g., Vitiello, et al. (1995) J. Clin. Invest. 95:341-349), peptide compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG") microspheres (see, e.g., Eldridge, et al. (1991) Molec. Immunol. 28:287-294; Alonso, et al. (1994) Vaccine 12:299-306; Jones, et al. (1995) Vaccine 13:675-681), peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e.g., Takahashi, et al. (1990) Nature 344:873- 875; Hu, et al. (1998) Clin. Exp. Immunol. 113:235-243), multiple antigen peptide systems (MAPs) (see, e.g., Tam (1988) Proc. Nat'l Acad. Sci. USA 85:5409-5413; Tam (1996) J. Immunol. Meth. 196:17-32), peptides formulated as multivalent peptides; peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery vectors (Perkus, et al., p. 379, inKaufmann (ed. 1996) Concepts in Vaccine Development de Gruyter; Chakrabarti, et al. (1986) Nature 320:535-537; Hu, et al. (1986) Nature 320:537-540; Kieny, et al. (1986) Bio/Technology 4:790-795;
Top, et al. (1971) J. Infect. Dis. 124:148-154; Chanda, et al. (1990) Virology 175:535- 547), particles of viral or synthetic origin (see, e.g., Kofler, et al. (1996) J. hnmunol. Meth. 192:25-35; Eldridge, et al. (1993) Sem. Hematol. 30:16-24; Falo, et al. (1995) Nature Med. 1:649-653), adjuvants (Wanen, et al. (1986) Ann. Rev. hnmunol. 4:369- 388; Gupta, et al. (1993) Vaccine 11 :293-306), liposomes (Reddy, et al. (1992) J. Immunol. 148:1585-1589; Rock (1996) Immunol. Today 17:131-137), or naked or particle absorbed cDNA (Ulmer, et al. (1993) Science 259:1745-1749; Robinson, et al. (1993) Vaccine 11 :957-960; Shiver, et al., p 423, in Kaufmann (ed. 1996) Concepts in Vaccine Development de Gruyter; Cease and Berzofsky (1994) Ann. Rev. Immunol. 12:923-989; and Eldridge, et al. (1993) Sem. Hematol. 30:16-24).
Toxin-targeted delivery technologies, also known as receptor mediated targeting, such as those of Avant hnmunotherapeutics, Inc. (Needham, MA) may also be used.
Vaccine compositions often include adjuvants. Many adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Certain adjuvants are commercially available as, e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A; and quil A. Cytokines, such as GM-CSF, interleukin-2, -7, -12, and other like growth factors, may also be used as adjuvants.
Vaccines can be administered as nucleic acid compositions wherein DNA or RNA encoding one or more of the polypeptides, or a fragment thereof, is administered to a patient. See, e.g., Wolff, et al. (1990) Science 247:1465-1468 as well as US Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720; and in more detail below. Examples of DNA-based delivery technologies include "naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated ("gene gun") or pressure-mediated delivery (see, e.g., US Patent No. 5,922,687). For therapeutic or prophylactic immunization purposes, the peptides of the invention can be expressed by viral or bacterial vectors. Examples of expression vectors include attenuated viral hosts, such as vaccinia or fowlpox. This approach involves the use of vaccinia virus, e.g., as a vector to express nucleotide sequences that encode cancer polypeptides or polypeptide fragments. Upon introduction into a host, the recombinant vaccinia viras expresses the immunogenic peptide, and thereby elicits an immune response. Vaccinia vectors and methods useful in immunization protocols are described, e.g., in US Patent No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). See Stover, et al. (1991) Nature 351:456-460. A wide variety of other vectors are available for therapeutic administration or immunization, e.g., adeno and adeno-associated virus vectors, refroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like. See, e.g., Shata, et al. (2000) Mol. Med. Today 6:66-71; Shedlock, et al. (2000) J. Leukoc. Biol. 68:793-806; and Hipp, et al. (2000) hi Vivo 14:571-85.
Methods for the use of genes as DNA vaccines are well known, and include placing a cancer gene or portion of a cancer gene under the control of a regulatable promoter or a tissue-specific promoter for expression in a soft tissue sarcoma cancer patient. The soft tissue sarcoma cancer gene used for DNA vaccines can encode full- length soft tissue sarcoma cancer proteins, but more preferably encodes portions of the cancer proteins including peptides derived from the cancer protein. In one embodiment, a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from a soft tissue sarcoma cancer gene. For example, soft tissue sarcoma cancer-associated genes or sequence encoding subfragments of a soft tissue sarcoma cancer protein are introduced into expression vectors and tested for their immunogenicity in the context of Class I MHC and an ability to generate cytotoxic T cell responses. This procedure provides for production of cytotoxic T cell responses against cells which present antigen, including intracellular epitopes.
In one embodiment, the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine. Such adjuvant molecules include cytokines that increase the immunogenic response to the soft tissue sarcoma cancer polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are available.
In another embodiment soft tissue sarcoma cancer genes find use in generating animal models of soft tissue sarcoma cancer. When the soft tissue sarcoma cancer gene identified is repressed or diminished in cancer tissue, gene therapy technology, e.g., wherein antisense RNA directed to the soft tissue sarcoma cancer gene will also diminish or repress expression of the gene. Animal models of soft tissue sarcoma cancer find use in screening for modulators of a soft tissue sarcoma cancer-associated sequence or modulators of soft tissue sarcoma cancer. Similarly, transgenic animal technology including gene knockout technology, e.g., as a result of homologous recombination with an appropriate gene targeting vector, will result in the absence or increased expression of the soft tissue sarcoma cancer protein. When desired, tissue- specific expression or knockout of the soft tissue sarcoma cancer protein may be necessary.
It is also possible that the soft tissue sarcoma cancer protein is overexpressed in soft tissue sarcoma cancer. As such, transgenic animals can be generated that overexpress the soft tissue sarcoma cancer protein. Depending on the desired expression level, promoters of various strengths can be employed to express the transgene. Also, the number of copies of the integrated transgene can be determined and compared for a detennination of the expression level of the transgene. Animals generated by such methods find use as animal models of soft tissue sarcoma cancer and are additionally useful in screening for modulators to treat soft tissue sarcoma cancer or to evaluate a therapeutic entity. Kits for Use in Diagnostic and/or Prognostic Applications
For use in diagnostic, research, and therapeutic applications suggested above, kits are also provided by the invention, h the diagnostic and research applications such kits may include at least one of the following: assay reagents, buffers, soft tissue sarcoma cancer-specific nucleic acids or antibodies, hybridization probes and or primers, antisense polynucleotides, ribozymes, dominant negative soft tissue sarcoma cancer polypeptides or polynucleotides, small molecules inhibitors of cancer- associated sequences, etc. A therapeutic product may include sterile saline or another pharmaceutically acceptable emulsion and suspension base. h addition, the kits may include instructional materials containing directions
(e.g., protocols) for the practice of the methods of this invention. While the instructional materials typically comprise written or printed materials they are not limited to such. A medium capable of storing such instructions and communicating them to an end user is contemplated by this invention. Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. Such media may include addresses to internet sites that provide such instructional materials.
The present invention also provides for kits for screening for modulators of soft tissue sarcoma cancer-associated sequences. Such kits can be prepared from readily available materials and reagents. For example, such kits can comprise one or more of the following materials: a soft tissue sarcoma cancer- associated polypeptide or polynucleotide, reaction tubes, and instructions for testing cancer-associated activity. Optionally, the kit contains biologically active soft tissue sarcoma cancer protein. A wide variety of kits and components can be prepared according to the present invention, depending upon the intended user of the kit and the particular needs of the user. Diagnosis would typically involve evaluation of a plurality of genes or products. The genes will be selected based on conelations with important parameters in disease which may be identified in historical or outcome data.
EXAMPLES
Example 1 Tissue Preparation, Labeling Chips, and Fingerprints Purify total RNA from tissue using TRIZOL Reagent
Estimate tissue weight. Homogenize tissue samples in 1ml of TRIZOL® (chemical reagents for use in isolating biological material from organic tissue) per 50mg of tissue using a Polytron 3100 homogenizer. The generator/probe used depends upon the tissue size. A generator that is too large for the amount of tissue to be homogenized will cause a loss of sample and lower RNA yield. Use the 20mm generator for tissue weighing more than 0.6g. If the working volume is greater than 2ml, then homogenize tissue in a 15ml polypropylene tube (Falcon 2059). Fill tube no greater than 10ml.
HOMOGENIZATION
Before using generator, it should have been cleaned after last usage by ranning it through soapy H20 and rinsing thoroughly. Run through with EtOH to sterilize. Keep tissue frozen until ready. Add TRIZOL® directly to frozen tissue then homogenize.
Following homogenization, remove insoluble material from the homogenate by centrifugation at 7500 x g for 15 min. in a Sorvall superspeed or 12,000 x g for 10 min. in an Eppendorf centrifuge at 4°C. Transfer the cleared homogenate to a new tube(s). The samples may be frozen now at -60 to -70°C (and kept for at least one month) or you may continue with the purification. PHASE SEPARATION
Incubate the homogenized samples for 5 minutes at room temperature. Add 0.2ml of chloroform per 1ml of TRIZOL® reagent used in the original homogenization. Cap tubes securely and shake tubes vigorously by hand (do not vortex) for 15 seconds.
Incubate samples at room temp, for 2-3 minutes. Centrifuge samples at 6500φm in a Sorvall superspeed for 30 min. at 4°C. (You may spin at up to 12,000 x g for 10 min. but you risk breaking your tubes in the centrifuge.) RNA PRECIPITATION
Transfer the aqueous phase to a fresh tube. Save the organic phase if isolation of DNA or protein is desired. Add 0.5ml of isopropyl alcohol per 1ml of TRIZOL® reagent used in the original homogenization. Cap tubes securely and invert to mix. Incubate samples at room temp, for 10 minutes. Centrifuge samples at 6500φm in Sorvall for 20min. at 4°C. RNA WASH
Pour off the supemate. Wash pellet with cold 75% ethanol. Use 1ml of 75% ethanol per 1ml of TRIzol reagent used in the initial homogenization. Cap tubes securely and invert several times to loosen pellet. (Do not vortex). Centrifuge at <8000φm (<7500 x g) for 5 minutes at 4°C.
Pour off the wash. Carefully transfer pellet to an eppendorf tube (let it slide down the tube into the new tube and use a pipet tip to help guide it in if necessary). Depending on the volumes you are working with, you can decide what size tube(s) you want to precipitate the RNA in. When I tried leaving the RNA in the large 15ml tube, it took so long to dry (i.e. it did not dry) that I eventually had to transfer it to a smaller tube. Let pellet dry in hood. Resuspend RNA in an appropriate volume of DEPC H 0. Try for 2-5ug/ul. Take absorbance readings. Purify poly AX mRNA from total RNA or clean up total RNA with Qiagen ' s RNeasy kit
Purification of poly A+ mRNA from total RNA. Heat oligotex suspension to 37°C and mix immediately before adding to RNA. Incubate Elution Buffer at 70°C. Warm up 2 x Binding Buffer at 65°C if there is precipitate in the buffer. Mix total RNA with DEPC-treated water, 2 x Binding Buffer, and Oligotex according to Table 2 on page 16 of the Oligotex Handbook. Incubate for 3 minutes at 65°C. Incubate for 10 minutes at room temperature.
Centrifuge for 2 minutes at 14,000 to 18,000 g. If centrifuge has a "soft setting," then use it. Remove supernatant without disturbing Oligotex pellet. A little bit of solution can be left behind to reduce the loss of Oligotex. Save sup until certain that satisfactory binding and elution of poly A+ mRNA has occuned. Gently resuspend in Wash Buffer OW2 and pipet onto spin column. Centrifuge the spin column at full speed (soft setting if possible) for 1 minute.
Transfer spin column to a new collection tube and gently resuspend in Wash Buffer OW2 and centrifuge as describe herein.
Transfer spin column to a new tube and elute with 20 to 100 ul of preheated (70°C) Elution Buffer. Gently resuspend Oligotex resin by pipetting up and down. Centrifuge as above. Repeat elution with fresh elution buffer or use first eluate to keep the elution volume low. Read absorbance, using diluted Elution Buffer as the blank. Before proceeding with cDNA synthesis, the mRNA must be precipitated. Some component leftover or in the Elution Buffer from the Oligotex purification procedure will inhibit downstream enzymatic reactions of the mRNA. Ethanol Precipitation
Add 0.4 vol. of 7.5 M NH4OAc + 2.5 vol. of cold 100% ethanol. Precipitate at -20°C 1 hour to overnight (or 20-30 min. at -70°C). Centrifuge at 14,000-16,000 x g for 30 minutes at 4°C. Wash pellet with 0.5ml of 80%ethanol (-20°C) then centrifuge at 14,000-16,000 x g for 5 minutes at room temperature. Repeat 80% ethanol wash. Dry the last bit of ethanol from the pellet in the hood. (Do not speed vacuum dry). Suspend pellet in DEPC H20 at lug/ul concentration. Clean up total RNA using Qiagen 's RNeasy kit
Add no more than lOOug to an RNeasy column. Adjust sample to a volume of lOOul with RNase-free water. Add 350ul Buffer RLT then 250ul ethanol (100%) to the sample. Mix by pipetting (do not centrifuge) then apply sample to an RNeasy mini spin column. Centrifuge for 15 sec at >10,000φm. If concerned about yield, re-apply flowthrough to column and centrifuge again.
Transfer column to a new 2-ml collection tube. Add 500ul Buffer RPE and centrifuge for 15 sec at >10,000φm. Discard flowthrough. Add 500ul Buffer RPE and centrifuge for 15 sec at >10,000φm. Discard flowthrough then centrifuge for 2 min at maximum speed to dry column membrane. Transfer column to a new 1.5-ml collection tube and apply 30-50ul of RNase-free water directly onto column membrane. Centrifuge 1 min at >10,000 φm. Repeat elution.
Take absorbance reading. If necessary, ethanol precipitate with ammonium acetate and 2.5X volume 100%) ethanol.
Make cDNA using Gibco 's "Superscript Choice System for cDNA Synthesis" kit First Strand cDNA Synthesis
Use 5ug of total RNA or lug of polyA+ mRNA as starting material. For total RNA, use 2ul of Superscript RT. For polyA+ mRNA, use lul of Superscript RT. Final volume of first strand synthesis mix is 20ul. RNA must be in a volume no greater than lOul. Incubate RNA with lul of lOOpmol T7-T24 oligo for 10 min at 70C. On ice, add 7 ul of: 4ul 5X 1st Strand Buffer, 2ul of 0.1 M DTT, and 1 ul of lOmM dNTP mix. h cubate at 37C for 2 min then add Superscript RT Incubate at 37C for 1 hour. Second Strand Synthesis
Place 1st strand reactions on ice. Add: 9M DEPC H20
30ul 5X 2nd Strand Buffer 3ul lOmM dNTP mix lul lOU/ul E.coli DNA Ligase
4ul lOU/ul E.coli DNA Polymerase lul 2U/ul RNase H
Make the above into a mix if there are more than 2 samples. Mix and incubate
2 hours at 16C.
Add 2ul T4 DNA Polymerase. Incubate 5 min at 16C. Add lOul of 0.5M EDTA
Clean up cDNA Phenol:Chloroform:Isoamyl Alcohol (25:24:1) purification using Phase-Lock gel (PLG) tubes.
Centrifuge PLG tubes for 30 sec at maximum speed. Transfer cDNA mix to PLG tube. Add equal volume of phenol:chloroform:isoamyl alcohol and shake vigorously (do not vortex). Centrifuge 5 minutes at maximum speed. Transfer top aqueous solution to a new tube. Ethanol precipitate: add 7.5X 5M NH4Oac and 2.5X volume of 100% ethanol. Centrifuge immediately at room temp, for 20 min, maximum speed. Remove sup then wash pellet 2X with cold 80% ethanol. Remove as much ethanol wash as possible then let pellet air dry. Resuspend pellet in 3ul RNase-free water. In vitro Transcription (IVT) and labeling with biotin
Pipet 1.5ul of cDNA into a thin-wall PCR tube. Make NTP labeling mix:
Combine at room temperature :2ul T7 lOxATP (75mM) (Ambion)
2ul T7 lOxGTP (75mM) (Ambion) 1.5ul T7 lOxCTP (75mM) (Ambion)
1.5ul T7 1 OxUTP (75mM) (Ambion) 3.75ul 10mM Bio-ll-UTP (Boehringer-
Mannheiin/Roche or Enzo) 3.75ul lOmM Bio- 16-CTP (Enzo) 2ul 1 Ox T7 transcription buffer (Ambion) 2ul lOx T7 enzyme mix (Ambion) Final volume of total reaction is 20ul. Incubate 6 hours at 37C in a PCR machine. RNeasy clean-up of IVT product Follow previous instructions for RNeasy columns or refer to Qiagen' s RNeasy protocol handbook. cRNA will most likely need to be ethanol precipitated. Resuspend in a volume compatible with the fragmentation step. Fragmentation 15 ug of labeled RNA is usually fragmented. Try to minimize the fragmentation reaction volume; a 10 ul volume is recommended but 20 ul is all right. Do not go higher than 20 ul because the magnesium in the fragmentation buffer contributes to precipitation in the hybridization buffer.
Fragment RNA by incubation at 94 C for 35 minutes in 1 x Fragmentation buffer.
5 x Fragmentation buffer: 200 mM Tris-acetate, pH 8.1 500 mM KOAc 150 mM MgOAc
The labeled RNA transcript can be analyzed before and after fragmentation. Samples can be heated to 65C for 15 minutes and electrophoresed on 1% agarose/TBE gels to get an approximate idea of the transcript size range Hybridization 200 ul (lOug cRNA) of a hybridization mix is put on the chip. If multiple hybridizations are to be done (such as cycling through a 5 chip set), then it is recommended that an initial hybridization mix of 300 ul or more be made. Hybrization Mix: fragment labeled RNA (50ng/ul final cone.) 50 pM 948-b control oligo 1.5 pM BioB
5 pM BioC 25 pM BioD 100 pM CRE 0.1 mg/ml herring sperm DNA 0.5mg/ml acetylated BSA to 300 ul with lxMES hyb. buffer The instruction manuals for the products used herein are incoφorated herein in their entirety. Labeling Protocol
Hybridization reaction:
Start with non-biotinylated F T (purified by RNeasy columns) (see example 1 for steps from tissue to IVT) IVT antisense RNA; 4 μg: μl Random Hexamers (1 μg/μl): 4 μl
H2O: μl
14 μl
- Incubate 70°C, 10 min. Put on ice.
Reverse transcription:
5X First Strand (BRL) buffer: 6 μl
0.1 M DTT: 3 μl
50X dNTP mix: 0.6 μl
H2O: 2.4 μl
Cy3 or Cy5 dUTP (ImM): 3 μl
SS RT II (BRL): l μl
16 μl
- Add to hybridization reaction. - Incubate 30 min., 42°C.
- Add 1 μl SSII and let go for another hour. Put on ice.
- 50X dNTP mix (25mM of cold dATP, dCTP, and dGTP, lOmM of dTTP: 25 μl each of lOOmM dATP, dCTP, and dGTP; 10 μl of lOOmM dTTP to 15 μl H2O. dNTPs from Pharmacia) RNA degradation:
86 μl H2O
- Add 1.5 μl IM NaOH/ 2mM EDTA, incubate at 65°C, 10 min. 10 μl 1 ON NaOH 4 μl 50mM EDTA U-Con 30
500 μl TE/sample spin at 7000g for 10 min, save flow through for purification Qiagen purification :
-suspend u-con recovered material in 500μl buffer PB -proceed w/ normal Qiagen protocol DNAse digest:
- Add 1 μl of 1/100 dil of DNAse/30μl Rx and incubate at 37°C for 15 min. -5 min 95°C to denature enzyme
Sample preparation :
- Add:
- Cot-1 DNA: 10 μl 50X dNTPs: l μl 20X SSC: 2.3 μl
Na pyro phosphate: 7.5 μl lOmg/ml Herring sperm DNA lul of 1/10 dilution 21.8 final vol.
- Dry down in speed vac. - Resuspend in 15 μl H 0.
- Add 0.38 μl 10% SDS.
- Heat 95°C, 2 min.
- Slow cool at room temp, for 20 min.
Put on slide and hybridize overnight at 64°C. Washing after the hybridization:
3X SSC/0.03% SDS: 2 min. 37.5 mis 20X SSC+0.75mls 10% SDS in 250mls
H2O
IX SSC: 5 min. 12.5 mis 20X SSC in 250mls H2O
0.2X SSC: 5 min. 2.5 mis 20X SSC in 250mls H2O Dry slides in centrifuge, 1000 RPM, lmin.
Scan at appropiate PMT's and channels. Example 2: Gene Chip Analysis Molecular profiles of various normal and soft tissue sarcoma cancer tissues were determined and analyzed using gene chips. RNA was isolated and gene chip analysis was performed as described above (Glynne, et al. (2000) Nature 403:672- 676; Zhao, et al. (2000) Genes Dev. 14:981-993). The results are shown in the tables and figures that follow. These soft tissue sarcoma (STSD) associated sequences are identified in the tables by Genbank Accession numbers and gene titles. As indicated, some of the Accession numbers include expression sequence tags (ESTs). Thus, in one embodiment herein, genes within an expression profile, also termed expression profile genes, include ESTs and are not necessarily full length.
TABLE IA
Pkey: Unique Eos probeset identifier number
Gene name : Unigene gene title
Accession: Exemplar Accession number, Genbank accession number
UniGene : Unigene number
RATIO: 95th percentile of chondrosarcomas AIs divided by the 50th percentile of normal tissue AIs , where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID #: Nucleic acid and prσte n sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
424687 matrix metalloproteinase 9 (gelatinase J05070 Hs.151738 48.5 1986 1987 6289
417153 collagen, type II, alpha 1 (primary ost X57010 Hs.81343 43.3 1084 10855625
422867 cartilage oligomeric matrix protein (ps L32137 Hs.1584 29.0 1751 17526122
428305 cartilage linking protein 1 AA446628 Hs.2799 22.1 2426 6607
422871 collagen, type XI, alpha 2 AL031228 Hs.121509 21.9 1753 17546123
424800 MyoD family inhibitor AL035588 Hs.153203 21.5 200220036300
413778 myosin, light polypeptide 2, regulatory AA090235 Hs.75535 17.6 740 5356
441134 cellular retinoic acid-binding protein W29092 Hs.346950 17.0 3500 7475
431553 cartilage linking protein 1 X78075 Hs.2799 16.7 2792 6874
417866 collagen, type XI, alpha 1 AW067903 Hs.82772 15.7 1162 5685
425154 collagen, type IX, alpha 1 NM 001851 Hs.154850 15.3 20552056 6339
428748 Ksp37 protein AW593206 Hs.98785 15.2 2468 6638
417070 titin 219077 Hs.172004 15.0 1070 5614
425545 Homo sapiens, clone MGC:12401, mRNA, co N98529 Hs.158295 13.9 2114 6379
403088 NM_003319*:Homo sapiens titin (TTN), mR 13.7 4707
428087 troponin C2, fast AA100573 Hs.182421 13.4 2396 6582
440274 scrapie responsive protein 1 R24595 Hs.7122 13.2 3464 7443
404977 Insulin-like growth factor 2 (somatomed 13.1 4766
412519 troponin T1, skeletal, slow AA196241 Hs.73980 12.7 598 5244
407245 titin X90568 Hs.172004 12.7 132 1334881
427474 aggrecan 1 (chondroitin sulfate proteog U13192 Hs.2159 12.6 2334 6532
435013 N _020142:Homo sapiens NADH:ubiquinone H91923 Hs.110024 12.5 3096 7115
452838 preferentially expressed antigen in mel U65011 Hs.30743 12.5 43574358 8188
410621 titin AA194329 Hs.172004 12.2 481 5149
422887 ESTs AI751848 Hs.49215 12.1 1755 6124
432239 matrix metalloproteinase 13 (collagenas X81334 Hs.2936 12.0 285628576921
427335 G antigen 7B AA448542 Hs.278444 11.6 2317 6520
432481 intron of collagen, type XI, alpha 1 AW451645 Hs.151504 11.4 2876 6938
432268 3'-phosphoadenosine 5'-phosphosulfate s BE311856 Hs.274230 11.4 2861 6925
405704 NM 001844*:Homo sapiens collagen, type 11.4 4794
448204 ESTs AI475124 Hs.170561 11.2 3988 7887
456115 titin F01082 Hs.172004 10.8 4515 8320
440042 ESTs AI073387 Hs.133898 10.5 3448 7430
427747 serine/threonine kinase 12 AW411425 Hs.180655 10.5 2365 6557
429329 Homo sapiens pannexin 3 (PANX3) AA456140 Hs.99235 10.4 2547 6699
408349 homeo box CIO BE546947 Hs.44276 10.2 213 4949
416373 ESTs, Weakly similar to S12658 cysteine AA195845 Hs.73680 10.1 996 5559
446619 secreted phosphoprotein 1 (osteopontin, AU076643 Hs.313 9.9 3861 7782
443802 KIAA1291 protein AW504924 Hs.9805 9.9 3647 7609
437330 Homo sapiens mRNA; cDNA DKFZp761J11121 ( AL353944 Hs.50115 9.9 3253 7250
428698 KIAA1866 protein AA852773 Hs.334838 9.9 2463 6635
409200 KIAA0076 gene product AL042914 Hs.51039 9.8 325 5037
416491 parathyroid hormone receptor 1 U17418 Hs.1019 9.8 1005 1006 5567
406707 myosin, heavy polypeptide 2, skeletal m S73840 Hs.931 9.4 61 624829
424408 collagen, type V, alpha 1 AI754813 Hs.146428 9.4 1943 6260
413011 biglycan AW068115 Hs.821 9.4 669 5302
414152 thrombospondin 4 NM 003248 Hs.75774 9.1 7827835391
426752 titin X69490 Hs.172004 9.1 22662267 6482
426300 delta-like homolog (Drosophila) U15979 Hs.169228 9.1 21962197 6437
426370 sortilin 1 R98288 Hs.281706 8.8 2215 6449
421552 secreted frizzled-related protein 4 AF026692 Hs.105700 8.8 1559 1560 5982
444381 hypothetical protein BC014245 BE387335 Hs.283713 8.7 3697 7652
417308 K1AA0101 gene product H60720 Hs.81892 8.7 1094 5634
452242 gycosyltransferase R50956 Hs.159993 8.7 4305 8145
406704 myosin, heavy polypeptide 7, cardiac mu M21665 Hs.929 8.6 55564826
417930 Homo sapiens mRNA for KIAA1870 protein, H81136 Hs.334604 8.4 1169 5691
432874 melanoma inhibitory activity W94322 Hs.279651 8.3 2913 6968
433513 ESTs AI566356 Hs.171437 8.2 2985 7024
409858 trinucleotide repeat containing 5 NM_006586 Hs.56828 8.2 391 3925084
443426 chromosome 20 open reading frame 1 AF098158 Hs.9329 8.2 3621 36227586 453665 ESTs, Weakly similar to SFRBJHUMAN SPLI AA626250 Hs.326184 8.1 4434 8253
407619 collagen, type IX, alpha 2 AL050341 Hs.37165 8.1 146 1474892
417849 nidogen 2 AW291587 Hs.82733 8.0 1161 5684
421967 interieukin 17B AA476704 Hs.110040 8.0 1621 6027 412129 troponin T3, skeletal, fast M21984 Hs.73454 8.0 571 5725222
429921 collagen, type XI, alpha 1 AA526911 Hs.82772 7.9 2620 6749
419875 proenkephalin AA853410 Hs.93557 7.9 1391 5859
419741 Ubiquitin carrier protein E2-C NM_007019 Hs.93002 7.9 1379 13805850
429166 KIAA1270 protein AB033096 Hs.197668 7.8 25222523 6679 431103 pleiotrophin (heparin binding growth fa M57399 Hs.44 7.8 274827496840
408482 adenosine A2b receptor NM 000676 Hs.45743 7.7 226 2274959
406964 FGENES predicted novel secreted protein M2Ϊ305 7.7 87884847
434449 hypothetical protein FLJ22041 similar t AW953484 Hs.3849 7.7 3057 7083
450778 solute carrier family 29 (nucleoside tr U81375 Hs.25450 7.6 4191 41928055 422640 troponin C, slow M37984 Hs.118845 7.6 1718 1719 6099
409327 collagen, type IX, alpha 3 L41162 Hs.53563 7.6 341 3425047
416658 fibrillin 2 (congenital contractural ar U03272 Hs.79432 7.5 1020 1021 5577
412978 homeo box Cδ A1431708 Hs.820 7.5 665 5298
409169 (clone PWHLC2-24) myosin light chain 2 F00991 Hs.50889 7.5 316 5029 449378 ESTs AW664026 Hs.59892 7.5 4085 7967
418883 acid phosphatase 5, tartrate resistant BE387036 Hs.1211 7.5 1281 5774
432538 male-enhanced antigen BE258332 Hs.278362 7.4 2884 6945
453060 hypothetical protein MGC15754 AW294092 Hs.21594 7.3 4386 8213
420462 chondromodulin I precursor AF050147 Hs.97932 7.3 14541455 5908 403071 NM_003319*:Homo sapiens titin (TTN), mR 7.3 4702
426991 Homo sapiens cDNA FLJ10674 fis, clone N AK001536 Hs.214410 7.3 22946502
417435 carbonic anhydrase III, muscle specific NM 005181 Hs.82129 7.2 112111225655
438913 ESTs AI380429 Hs.172445 7.2 33647347
453935 ESTs AI633770 Hs.42572 7.2 44708281 422684 H2A histone family, member Z BE561617 Hs.119192 7.2 17266105
444784 ectonucleotide pyrophosphatase/phosphod D12485 Hs.11951 7.2 372437257673
444232 hypothetical protein DKFZp761H221 W56010 Hs.347297 7.1 36877644
425071 deiodinase, iodothyronine, type II NM_013989Hs.154424 7.1 204320446330
422633 enolase 3, (beta, muscle) X56832 Hs.118804 7.0 171617176098 453271 ESTs AA903424 Hs.6786 7.0 44098232
452402 peroxisome proliferative activated rece AI138530 Hs.22216 7.0 43278162
421579 stem cell growth factor; lymphocyte sec NM 002975 Hs.105927 7.0 156715685987
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs.156346 7.0 209921006369
449969 Homo sapiens cDNA FU14337 fis, clone P AW295142 Hs.180187 6.9 41238001 419926 DKFZP586D2223 protein AW900992 Hs.93796 6.9 13965863
432596 matrilin 3 AJ224741 Hs.278461 6.9 288928906950
419452 PTK7 protein tyrosine kinase 7 U33635 Hs.90572 6.9 134013415821
448721 ESTs AI632123 Hs.371431 6.9 40297921
437352 hypothetical protein DKFZp434P0531 AL353957 Hs.284181 6.8 325532567252 408831 endocrine regulator AF090114 Hs.48433 6.8 2662674992
426935 collagen, type I, alpha 1 NM 000088 Hs.172928 6.7 228822896498
434906 Homo sapiens, clone 1MAGE:4053965, mRNA BE410573 Hs.283636 6.7 30907110
405946 Target Exon 6.7 4798
450701 hypothetical protein XP J98151 (leucine H39960 Hs.288467 6.7 41838048 403074 NMJ03319*:Homo sapiens titin (TTN), mR 6.6 4703
411296 growth suppressor 1 BE207307 Hs.10114 6.6 5245183
452281 Homo sapiens cDNA FLJ11041 fis, clone P T93500 Hs.28792 6.6 43098149
421535 phosphoribosylformylglycinamidine synth AB002359 Hs.105478 6.5 155715585981
427585 collagen, type X, alpha 1 (Sch id metap D31152 Hs.179729 6.5 23496543 428981 ESTs, Weakly similar to ALU2_HUMAN ALU BE313077 Hs.93135 6.5 24976660
428342 Homo sapiens cDNA FLJ 13458 fis, clone P AI739168 Hs.349283 6.5 24326611
436608 down syndrome critical region protein D AA628980 Hs.192371 6.5 32057207
444165 hypothetical protein FLJ11236 AL137443 Hs.10441 6.5 36827639
419745 slug (chicken homolog), zinc finger pro AF042001 Hs.93005 6.4 138113825851 438746 Human melanoma-associated antigen p97 ( AI885815 Hs.184727 6.4 33537337
449048 similar to S68401 (cattle) glucose indu Z45051 Hs.22920 6.4 40617945
441553 ESTs AA281219 Hs.121296 6.4 35257498
437696 hypothetical protein dJ37E16.5 Z83844 Hs.5790 6.4 32817274
410929 ESTs H47233 Hs.30643 6.4 5045166 443105 chondroitin sulfate proteoglycan 4 (mel X96753 Hs.9004 6.3 360036017568
446051 ephrin-A3 BE048061 Hs.37054 6.3 38167744
400440 nebulin X83957 Hs.83870 6.3 24254627
429359 matrix metalloproteinase 14 (membrane-i W00482 Hs.2399 6.3 25516702
433001 clone HQ0310 PRO0310p1 AF217513 Hs.279905 6.3 292329246977 415989 ESTs AI267700 Hs.351201 6.3 9625530
452826 peroxisomal biogenesis factor 6 BE245286 Hs.301636 6.3 43538184
434352 small muscle protein, X-linked AF129505 Hs.86492 6.3 304730487075
409142 SMC4 (structural maintenance of chromos AL136877 Hs.50758 6.3 3123135027
412709 KIAA0027 protein AL022327 Hs.74518 6.2 6316325269 411789 Adlican AF245505 Hs.72157 6.2 5535545207
453392 SRY (sex determining region Y)-box 11 U23752 Hs.32964 6.2 441644178239 440028 ESTs, Weakly similar to T17227 hypothet AW473675 Hs.367649 6.2 3446 7428
416768 regenerating islet-derived 1 alpha (pan AA363733 Hs.1032 6.2 1030 5583
422627 transforming growth factor, beta-induce BE336857 Hs.118787 6.2 1715 6097
443610 mitochondrial ribosomal protein S18A AW248314 Hs.9622 6.2 3628 7591
421307 Homo sapiens mRNA; cDNA DKFZp434B0425 ( BE539976 Hs.103305 6.1 1528 5963
426413 gb:EST90805 Synovial sarcoma Homo sapie AA377823 6.1 2219 6453
424086 lysyl oxidase AI351010 Hs.102267 6.1 1896 6227
450087 MUM2 protein BE293180 Hs.24379 6.1 4133 8008
421155 lysyl oxidase H87879 Hs.102267 6.1 1512 5950
407604 collagen, type VIII, alpha 2 AW191962 Hs.353001 6.1 145 4891
437033 RNA polymerase I subunit AW248364 Hs.5409 6.1 3231 7230
427427 lectin, superfamily member 1 (cartilage AF077345 Hs.177936 6.0 23282329 6528
420005 ESTs AW271106 Hs.133294 6.0 1407 5871
453331 ESTs AI240665 Hs.352537 6.0 4413 8236
423785 Homo sapiens WWp2-like mRNA complete cd BE467186 Hs.333382 6.0 1849 6195
412719 ESTs AW016610 Hs.816 6.0 633 5270
425462 Homo sapiens cDNA; FLJ22382 fis, clone AI491852 Hs.46783 5.9 2106 6373
437898 ESTs W81260 Hs.43410 5.9 3293 7286
417944 collagen, type V, alpha 2 AU077196 Hs.82985 5.9 1172 5693
439737 Homo sapiens mRNA full length insert cD AI751438 Hs.41271 5.9 3427 7410
420162 cyclin-dependent kinase 4 BE378432 Hs.95577 5.9 1422 5883
449722 cyclin B1 BE280074 Hs.23960 5.9 4112 7990
412140 RAB6 interacting, kinesin-like (rabkine AA219691 Hs.73625 5.8 573 5223
421823 ESTs N40850 Hs.28625 5.8 1600 6011
451149 RNA binding motif protein 8B AL047586 Hs.10283 5.8 4214 8073
444371 forkhead box M1 BE540274 Hs.239 5.8 3696 7651
427157 thymine-DNA glycosylase U51166 Hs.173824 5.8 23052306 6511
429415 procollagen C-endopeptidase enhancer NM 002593 Hs.202097 5.8 255725586706
431556 sarcospan (Kras oncogene-associated gen AF016028 Hs.183428 5.8 279327946875
419987 osteomodulin NM 005014 Hs.94070 5.8 1402 14035868
412646 transmembrane protein (63kD), endoplasm NM_006825Hs,74368 5.8 6236245262
412939 eukaryotic translation elongation facto AW411491 Hs.75069 5.8 657 5292
443184 ESTs AI638728 Hs.135159 5.8 3607 7574
426462 dermatan sulphate proteoglycan 3 U59111 Hs.169993 5.7 22302231 6460
428269 ESTs, Moderately similar to ZN91JHUMAN W35195 Hs.95659 5.7 2416 6598
444301 asporin (LRR class 1) AK000136 Hs.10760 5.7 3691 36927647
439253 ESTs AF086064 Hs.337696 5.7 3387 7370
409731 thymosin, beta, identified in neuroblas AA125985 Hs.56145 5.7 386 5080
422087 matrix metalloproteinase 2 (gelatinase X58968 Hs.111301 5.7 1641 6040
414477 amplified in osteosarcoma U41635 Hs.76228 5.7 8228235425
410102 ESTs; homologue of PEM-3 [Ciona savigny AW248508 Hs.279727 5.7 422 5107
407740 ESTs AA295547 Hs.353519 5.7 156 4900
452973 ESTs H88409 Hs.40527 5.7 4375 8203
417900 CDC20 (cell division cycle 20, S. cerev BE250127 Hs.82906 5.7 1165 5688
414219 ALL1-fused gene from chromosome 1q W20010 Hs.75823 5.7 789 5397
409686 Homo sapiens mRNA; cDNA DKFZp434L0827 ( AK000002 Hs.55879 5.7 376377 5073
426067 ESTs AW664691 Hs.97053 5.6 2169 6416
417160 proteolipid protein 1 (Pelizaeus-Merzba N76497 Hs.355807 5.6 1086 5626
423961 periostin (OSF-2os) D13666 Hs.136348 5.6 187818796215
427871 Homo sapiens, clone IMAGE:3507281, mRNA AW992405 Hs.352406 5.6 2380 6568
431089 ESTs, Weakly similar to unknown protein BE041395 Hs.374629 5.6 2745 6838
410491 Homo sapiens clone 25218 mRNA sequence AA465131 Hs.64001 5.6 465 5138
433075 sortilin 1 NM 002959 Hs.351872 5.6 29362937 6987
407896 Zic family member 1 (odd-paired Drosoph D76435 Hs.41154 5.5 176 1774919
428862 SRY (sex determining region Y)-box 9 (c NM_000346 Hs.2316 5.5 248324846650
443883 serine (or cysteine) proteinase inhibit AA114212 Hs.9930 5.5 3653 7614
452862 ADAMTS2 (a disintegrin-like and metail AW378065 Hs.8687 5.5 4360 8190
452471 gb:RC-BT029-090199-079 BT029 Homo sapie AI903332 5.5 4335 8169
423073 MAD (mothers against decapentaplegic, D BE252922 Hs.123119 5.5 1777 6142
409893 minichromosome maintenance deficient (S AW247090 Hs.57101 5.5 397 5088
453597 myo-inositol 1 -phosphate synthase A1 BE281130 Hs.381118 5.5 4429 8249
439456 hypothetical protein FLJ20980 AI752409 Hs.109314 5.5 3400 7383
418533 myosin-binding protein C, fast-type NM 004533 Hs.85937 5.5 1253 12545754
437446 ESTs, Moderately similar to CA1C RAT CO AA788946 Hs.101302 5.5 3264 7259
419073 Homo sapiens cDNA FLJ12797 fis, clone N AW372170 Hs.183918 5.5 1296 5786
439108 synaptogyrin 3 AW163034 Hs.6467 5.5 3377 7360
436476 bHLH protein DEC2 AA326108 Hs.33829 5.4 3190 7195
414117 proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs.355807 5.4 777 5386
441362 RAD51 (S. cerevisiae) homolog (E coli R BE614410 Hs.23044 5.4 3512 7486
417796 ESTs AA206141 Hs.367818 5.4 1159 5682
406687 matrix metalloproteinase 11 (stromelysi M31126 Hs.352054 5.4 49504823
418054 lysyl oxidase-like 2 NM_002318 Hs.83354 5.4 1184 11855702
432691 mitogen-activated protein kinase 7 U29725 Hs.3080 5.4 289728986956
410687 lysyl oxidase-like 1 U24389 Hs.65436 5.4 4854865153
453941 Bloom syndrome U39817 Hs.36820 5.4 4471 44728282
432731 fibronectin 1 R31178 Hs.287820 5.4 2904 6961 430209 collagen, type V, alpha 3 AF177941 Hs.235368 5.3 265926606778
409041 Hypothetical protein, XP_051860 (KIAA11 AB033025 Hs.50081 5.3 2993005017
408901 hypothetical protein FLJ10468 AK001330 Hs.48855 5.3 2722734997
411078 CocoaCrisp A1222020 Hs.182364 5.3 5125172 457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs.32399 5.3 45438344
426058 Nedd-4-like ubiquitin-protein ligase U96114 Hs.333382 5.3 216621676414
431247 matrilin 4 AL021578 Hs.278489 5.3 276827696855
418140 microfibriilar-associated protein 2 BE613836 Hs.83551 5.3 11965713
452214 hypothetical protein FLJ10567 AK001429 Hs.380887 5.3 430043018141 422043 retinoic acid induced 1 AL133649 Hs.110953 5.3 162916306033
452683 progesterone membrane binding protein AI089575 Hs.374574 5.3 43418175
423811 homeo box C4 AW299598 Hs.50895 5.3 18546198
423225 Thy-1 cell surface antigen AA852604 Hs.125359 5.2 17866148
424308 minichromosome maintenance deficient (S AW975531 Hs.154443 5.2 19326250 436907 ESTs AA737171 Hs.131809 5.2 32267225
430393 estrogen-responsive B box protein BE185030 Hs.241305 5.2 26886798
433612 Homo sapiens Ku70-binding protein (KUB3 AF078164 Hs.61188 5.2 299129927030
441356 ESTs, Weakly similarto JC5024 UDP-gala BE384361 Hs.182885 5.2 35117485
447343 ESTs, Highly similar to S02392 alpha-2- AA256641 Hs.236894 5.2 39167828 445826 Homo sapiens mRNA; cDNA DKFZp586D0918 ( BE313754 Hs.13350 5.2 38007730
452873 hypothetical protein FLJ10385 AK001247 Hs.30922 5.2 436243638192
408202 DKFZP586L151 protein AA227710 Hs.43658 5.2 2024942
435256 cytokine-like protein C17 AF193766 Hs.13872 5.2 311631177133
412641 heatshock 90kD protein 1, beta M16660 Hs.74335 5.2 6206215260 430890 glypican 1 X54232 Hs.2699 5.2 273527366831
414358 ESTs AA476456 Hs.98969 5.2 8075412
442573 branched chain aminotransferase 1, cyto H93366 Hs.7567 5.2 35707541
412564 cardiac ankyrin repeat protein X83703 Hs.355934 5.2 6066075251
417791 ESTs AW965339 Hs.44269 5.1 11585681 422765 baculoviral IAP repeat-containing 5 (su AW409701 Hs.1578 5.1 17346110
416391 mesoderm specific transcript (mouse) ho AI878927 Hs.79284 5.1 9995562
421295 DC2 protein AW081061 Hs.103180 5.1 15245960
445564 KIAA1034 protein AB028957 Hs.12896 5.1 378437857718
417675 similar to murine leucine-rich repeat p AI808607 Hs.3781 5.1 11445670 447149 TAR (HIV) RNA-binding protein 2 BE299857 Hs.326 5.1 38937809
435284 Homo sapiens cDNA FLJ 11492 fis, clone H AA879470 Hs.96849 5.1 31187134
419488 nucleophosmin/nucleoplasmin 3 AA316241 Hs.90691 5.1 13425822
408829 heparan sulfate (glucosamine) 3-O-sulfo NM 006042 Hs.48384 5.1 2642654991
409262 hypothetical protein FLJ20624 AK000631 Hs.52256 5.1 3333345042 446142 ESTs AI754693 Hs.145968 5.1 38207748
418927 ESTs BE349635 Hs.190284 5.1 12845776
418283 cathepsin K (pycnodysostosis) S79895 Hs.83942 5.1 121012115724
428957 WNT1 inducible signaling pathway protei NM 003881 Hs.194679 5.1 249124926656
416322 pyrroline-5-carboxylate reductase 1 BE019494 Hs.79217 5.1 9895554 409361 sine oculis homeobox (Drosophila) homol NM 005982 Hs.54416 5.1 3443455049
414733 minichromosome maintenance deficient (S BE514535 Hs.77171 5.1 8605454
415885 KIAA0161 gene product D79983 Hs.78894 5.1 9539545524
444912 putative prostate cancer susceptibility AW247380 Hs.12124 5.0 37337679
448425 ESTs AI500359 Hs.371249 5.0 40047901 423292 nuclear RNA export factor 2 AK000423 Hs.306209 5.0 179117926152
437430 gene predicted from cDNA with a complet W44671 Hs.124 5.0 32617256
451999 DEAD/H (Asp-Glu-Ala-Asp/His) box polype AW176401 Hs.380623 5.0 42688115
418113 SRY (sex determining region Y)-box 4 AI272141 Hs.83484 5.0 11945711
445160 sine oculis homeobox (Drosophila) homol AI299144 Hs.101937 5.0 37487692 431411 hypothetical protein FLJ20343 AI929382 Hs.252692 5.0 27826866
431347 insulin-like growth factor 2 (somatomed AI133461 Hs.251664 5.0 27746859
452907 ESTs, Moderately similar to I54374 gene BE256966 Hs.31652 5.0 43688197
440211 ESTs AA872730 Hs.125229 5.0 34637442
436895 carbonic anhydrase XII AF037335 Hs.5338 5.0 322432257224 414883 CDC28 protein kinase 1 AA926960 Hs.348669 5.0 8855471
408135 methyltransferase-like 1 AA317248 Hs.42957 5.0 1944936
414038 hypothetical protein FLJ22439 BE242722 Hs.180040 5.0 7735382
411102 triadin AA401295 Hs.23926 5.0 5155175
433659 hypothetical protein FLJ10439 AK001301 Hs.3487 4.9 299829997035 433092 WAS protein family, member 2 A1936829 Hs.288908 4.9 29396989
433430 ESTs AI863735 Hs.369982 4.9 29777018
417605 regulator of G-protein signalling 3 AF006609 Hs.82294 4.9 113811395665
412490 Homo sapiens cDNA: FLJ22528 fis, clone AW803564 Hs.288850 4.9 5955242
437206 ESTs, Weaklysimilarto I38344 titin, c AW975934 Hs.172004 4.9 32457242 413434 Homo sapiens cDNA FLJ11416 fis, clone H N41759 Hs.287331 4.9 7185337
406706 myosin, heavy polypeptide 1, skeletal m X03740 Hs.231581 4.9 59604828
410611 KIAA1628 protein AW954134 Hs.20924 4.9 4805148
442295 Homo sapiens cDNA FLJ11469 fis, clone H AI827248 Hs.224398 4.9 35557527
439717 ESTs, ModeratelysimilartoALU1_HUMAN W94472 Hs.59529 4.9 34237406 451766 ephrin-B3 NM 001406 Hs.26988 4.9 425542568104
409243 KIAA1340 protein AB037761 Hs.51743 4.9 3283295039 407690 hypothetical protein FLJ14281 R47799 Hs.266957 4.9 150 4895
407025 Human unknown protein mRNA within the p U58658 Hs.356460 4.9 96974852
414812 monokine induced by gamma interferon X72755 Hs.77367 4.9 874 8755464
424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs.93135 4.9 1907 6235 446157 Homo sapiens cDNA: FLJ22562 fis, clone BE270828 Hs.131740 4.9 3821 7749
441944 Homo sapiens clone 23767 and 23782 mRNA AW855861 Hs.8025 4.9 3541 7513
411742 eukaryotic translation initiation facto AW247593 Hs.71819 4.9 549 5204
415702 gb:HSPD18414 HM3 Homo sapiens cDNA clon F28877 Hs.73680 4.9 942 5515
429500 hexabrachion (tenascin C, cytotactin) X78565 Hs.289114 4.9 257425756718 431183 KDEL (Lys-Asp-Glu-Leu) endoplasmic reti NM 006855 Hs.250696 4.8 275627576845
428409 ESTs AW117207 Hs.98523 4.8 2438 6616
451404 ESTs, Weakly similarto T17248 hypothet AA460775 Hs.6295 4.8 4229 8084
453115 ESTs, Moderately similar to JC5238 gala AW772041 Hs.18439 4.8 4392 8218
448950 CGI-152 protein AF288687 Hs.9275 4.8 40504051 7936 426509 pentaxin-related gene, rapidly induced M31166 Hs.2050 4.8 224322446468
451684 CDA14 AF216751 Hs.26813 4.8 424642478098
425196 carbonic anhydrase II AL037915 Hs.155097 4.8 2064 6345
412755 ESTs, Weakly similar to P4HAJHUMAN PROL BE144306 Hs.179891 4.8 637 5274
453393 ESTs AW956392 Hs.110376 4.8 4418 8240 428977 cyclin B2 AK001404 Hs.194698 4.8 2496 6659
419086 Kall ann syndrome 1 sequence NM 00216 Hs.89591 4.8 1300 1301 5789
447519 ESTs U46258 Hs.339665 4.8 3936 7844
414359 cadherin 11 , type 2, OB-cadherin (osteo M62194 Hs.75929 4.8 808 5413
438093 COP9 (constitutive photomorphogenic, Ar BE206885 Hs.6076 4.8 3303 7296 444670 hypothetical protein MGC5370 H58373 Hs.332938 4.8 3714 7666
409103 XAGE-1 protein AF251237 Hs.112208 4.7 3043055021
422809 hypothetical protein FLJ10549 AK001379 Hs.121028 4.7 1741 17426115
419762 ESTs AI608647 Hs.32374 4.7 1387 5855
421057 Homo sapiens cDNA: FLJ22063 fis, clone T58283 Hs.120638 4.7 1501 5940 419575 topoisomerase (DNA) III alpha U43431 Hs.91175 4.7 1355 13565831
408196 SRY (sex determining region Y)-box 22 AL034548 Hs.43627 4.7 1992004940 402408 NM_030920*:Homo sapiens hypothetical pr 4.7 4681 421778 actin related protein 2/3 complex, subu AA428000 Hs.283072 4.7 15916003
411894 GLI-Kruppel family member GLI3 (Greig c M57609 Hs.72916 4.7 5595605212 403285 Target Exon 4.7 4712
435099 flap structure-specific endonuclease 1 AC004770 Hs.4756 4.7 310431057123
413658 A kinase (PRKA) anchor protein 10 AA055369 Hs.372446 4.7 7345351
454119 uncoupling protein 4 BE549773 Hs.40510 4.7 44928300
415667 developmental^ regulated GTP-binding p F11582 Hs.78582 4.7 9355509 402672 Target Exon 4.7 4686
446517 phosphatidylethanolamine N-methyltransf BE382714 Hs.15192 4.7 38497772
437623 chromosome condensation-related SMC-ass D63880 Hs.5719 4.7 327532767269
447377 transcription factor AP-2 alpha X77343 Hs.334334 4.7 392039217831
425848 valyl-tRNA synthetase 2 BE242709 Hs.159637 4.7 21506402 448121 hypothetical protein DKFZp564F013 AL045714 Hs.128653 4.7 39797881
414961 myosin-binding protein H U27266 Hs.927 4.6 8968975479
403903 C5001632*:gi|10645308|gb|AAG21430.1|ACO 4.6 4731
444719 ESTs, Weakly similar to GGE1_HUMAN GAGE N40147 Hs.43879 4.6 37177668
418036 latent transforming growth factor beta Z37976 Hs.83337 4.6 118011815699 406976 gb:Human alpha-1 collagen type II gene, M60299 4.6 92934850
411852 ESTs, Weakly similar to T00329 hypothet AA528140 Hs.107515 4.6 5555208
421506 thymidine kinase 1 , soluble BE302796 Hs.105097 4.6 15505976
428344 Homo sapiens cDNA FLJ12425 fis, clone M AW449466 Hs.9299 4.6 24336612
448734 Homo sapiens mRNA; cDNA DKFZp564H1916 ( BE614070 Hs.326416 4.6 40317923 412014 ESTs, Weakly similarto A4601 O X-linked AI620650 Hs.43761 4.6 5665218
452436 ESTs, Moderately similar to A46010 X-li BE077546 Hs.31447 4.6 43308164
445373 ESTs, Weakly similar to DIA1_HUMAN DIAP AW962886 Hs.199316 4.6 37647703
413004 interleukin enhancer binding factor2, T35901 Hs.75117 4.6 6675300
442426 hypothetical protein MGC5370 AI373062 Hs.332938 4.6 35627534 408920 fibronectin leucine rich transmembrane AL120071 Hs.48998 4.6 2764999
425259 Homo sapiens mRNA; cDNA DKFZp564K143 (f AL 049280 Hs.145010 4.6 20756353
409096 sarcomeric muscle protein AA194412 Hs.50550 4.6 3025019
428279 ESTs, Weakly similar to A47582 B-cell g AA425310 Hs.155766 4.6 24176599
449510 ESTs AI653154 Hs.328147 4.6 40927974 422112 Lsm1 protein BE540240 Hs.111783 4.5 16496046
427217 ESTs AA399272 Hs.144341 4.5 23106514
412537 nuclear transcription factor Y, alpha AL031778 Hs.348999 4.5 601 5247
430411 bone gamma-carboxyglutamate (gla) prate X51699 Hs.2558 4.5 269126926800
407204 ESTs, Weakly similar to ALU1JHUMAN ALU R41933 Hs.140237 4.5 1214873 421114 ESTs, Weakly similar to I78885 serine/t AW975051 Hs.293156 4.5 15075946
408197 ESTs, Weakly similar to A4601 O X-linked AA282262 Hs.107410 4.5 2014941 436291 protein regulator of cytokinesis 1 BE568452 Hs.344037 4.5 31807185 414416 hypothetical protein MGC2721 AW409985 Hs.76084 4.5 8135417 407792 putative secreted ligand homologous to AI077715 Hs.39384 4.5 1624906 452461 transcription factor N78223 Hs.108106 4.5 43338167
436252 Homo sapiens cDNA FLJ 11562 fis, clone H AI539519 Hs.142827 4.5 31797184 422034 Ets2 repressor factor AC006486 Hs.333069 4.5 1627 16286032
432917 PRO0327 protein NM 014125 Hs.241517 4.5 291529166970
453299 ESTs W44626 Hs.30627 4.5 4411 8234
424265 hairy/enhancer-of-split related with YR AF173901 Hs.144287 4.5 1927 19286247 436481 HSPC150 protein similar to ubiquitin-co AA379597 Hs.5199 4.5 3192 7197
420197 ESTs, Weakly similar to A57291 cytokine AW139647 Hs.88134 4.5 1429 5889
420576 KIAA1858 protein AA297634 Hs.54925 4.5 1463 5914
409012 DKFZP434I216 protein AL117435 Hs.49725 4.5 293 2945013
419552 gb;zd30a08.s1 Soares_fetal_heart_NbHH19 W63730 Hs.379098 4.4 1350 5828 407239 leukocyte immunoglobulin-like receptor, AA076350 Hs.67846 4.4 129 4879
424330 Homo sapiens cDNA FLJ13596 fis, clone P AW073953 Hs.34054 4.4 1936 6253
417933 thy idylate synthetase X02308 Hs.82962 4.4 1170 1171 5692
447630 lymphoid enhancer-binding factor 1 AI660149 Hs.44865 4.4 3944 7851
404567 NM_015902*:Homo sapiens progestin indue 4.4 4752 439053 chaperonin containing TCP1, subunit 2 ( BE244588 Hs.6456 4.4 33747357
438982 ESTs, Weakly similar to A47582 B-cell g AW979101 Hs.291980 4.4 33727355
423575 intron of periostin (OSF-2os) C18863 Hs.163443 4.4 18206173
456816 hypothetical protein FLJ10647 AK001509 Hs.144391 4.4 453145328334
443778 Homo sapiens cDNA FLJ14207 fis, clone N AW964139 Hs.9741 4.4 36427605 430681 ESTs AW969675 Hs.291232 4.4 27196819
434652 bladder cancer overexpressed protein AF148713 Hs.125830 4.4 306630677092
435937 ESTs AA830893 Hs.119769 4.4 31647172
447381 Homo sapiens cDNA FLJ14459 fis, clone H A1377119 Hs.295362 4.4 39227832
427647 Homo sapiens cDNA FLJ20653 fis, clone K W19744 Hs.180059 4.4 23546548 424084 hypothetical protein FLJ23056 A1940675 Hs.20914 4.4 18956226
425274 minichromosome maintenance deficient (m BE281191 Hs.155462 4.4 20796356
412935 tubulin-specific chaperone c BE267045 Hs.75064 4.4 ' 6565291
422599 non-metastatic cells 1 , protein (NM23A) BE387202 Hs.118638 4.4 17106092
426363 transforming growth factor, beta 3 M58524 Hs.2025 4.4 221022116446 418156 nuclear receptor subfamily 1, group I, W17056 Hs.83623 4.4 11985715
453880 ESTs, Weakly similar to I38022 hypothet AI803166 Hs.135121 4.4 44588272
423739 ESTs AA398155 Hs.97600 4.4 18426190
439688 hypothetical protein FLJ12921 AW445181 Hs.209637 4.4 34187401
449037 Homo sapiens mRNA; cDNA DKFZp586F071 (f AL050125 Hs.22907 4.4 40607944 418677 SRY (sex determining region Y)-box 5 S83308 Hs.87224 4.4 126 12685764
433446 ESTs AW469546 Hs.122116 4.3 29797020 420044 ESTs AA253164 Hs.136294 4.3 14105873 417124 ESTs BE122762 Hs.25338 4.3 10825623
421777 HSPC037 protein BE562088 Hs.108196 4.3 15906002 430044 ESTs AA464510 Hs.152812 4.3 26426765
429973 ESTs AI423317 Hs.164680 4.3 26286756
410366 hypothetical protein AI267589 Hs.302689 4.3 4575133
425308 receptor tyrosine kinase-like orphan re M97639 Hs.155585 4.3 208720886362
442052 ESTs AW450515 Hs.128381 4.3 35467518 421848 collagen, type VI, alpha 1 X15880 Hs.108885 4.3 160216036013
424840 extra spindle poles, S. cerevisiae, horn D79987 Hs.153479 4.3 201120126306
417788 nuclear transcription factor Y, beta AI436699 Hs.84928 4.3 11575680
404561 trichorhinophalangeal syndrome I gene ( 4.3 4751
433447 neuronal pentraxin II U29195 Hs.3281 4.3 298029817021 428280 sarcospan (Kras oncogene-associated gen H05541 Hs.183428 4.3 24186600
406850 collagen, type I, alpha 1 AI624300 Hs.172928 4.3 704837
407730 splicing factor, arginine/serine-rich 9 AI457482 Hs.77608 4.3 1554899
426487 variable charge, Y chromosome AF000979 Hs.170076 4.3 224022416466
410036 calsequestrin 2 (cardiac muscle) R57171 Hs.57975 4.3 4125100 422452 Homo sapiens mRNA; cDNA DKFZp566J1846 ( AL110255 Hs.116808 4.3 16856073
421016 transcription factor 3 (E2A immunoglobu AA504583 Hs.101047 4.3 14975937
427458 ESTs, Weakly similar to LKHU proteoglyc BE208364 Hs.29283 4.3 23326530
442117 ESTs; hypothetical protein for IMAGE:44 AW664964 Hs.128899 4.3 35517523
425516 ESTs BE000707 Hs.353519 4.3 21106376 425398 hypothetical protein similar to tenasci AL049689 Hs.156369 4.3 210121026370
413053 ESTs, Moderately similarto KIAA1399 pr AW963263 Hs.65377 4.3 6745306
406837 immunoglobulin kappa constant R70292 Hs.156110 4.3 694836
423072 solute carrier family 12 (sodium/potass AI792946 Hs.123116 4.3 17766141
435124 ESTs AA725362 Hs.75514 4.3 31077125 410169 hypothetical protein MGC3047 AI373741 Hs.59384 4.3 4285112
436878 ESTs BE465204 Hs.47448 4.3 32237223
429638 kinectin 1 (kinesin receptor) AI916662 Hs.21 577 4.3 25956731
425532 KIAA0446 gene product AB007915 Hs.158286 4.3 211221136378
424905 NIMA (never in mitosis gene a)-related NM 002497 Hs.153704 4.3 202220236315 451448 homolog of yeast MOG1 AW952599 Hs.13605 4.3 42318086
432101 EphA3 AI918950 Hs.123642 4.3 28416909
410701 RNA binding motif protein 8A AF198620 Hs.10283 4.3 4874885154
426817 Homo sapiens mRNA; cDNA DKFZp564C0671 ( AL122088 Hs.172627 4.3 22766488
424560 protein predicted by clone 23733 AA158727 Hs.150555 4.2 19726279 417404 pleckstrin homology-like domain, family NM 007350 Hs.82101 4.2 111011115648
454090 gb:MRO-CT0064-100899-002-h09 CT0064 Horn AW062462 4.2 44908298 405452 Target Exon 4.2 4784
406947 DNA-binding protein amplifying expressi L10403 Hs.3134 4.2 85864846
414312 ESTs AA155694 Hs.191060 4.2 8005407
435373 ESTs AW665538 Hs.117689 4.2 31217137 425514 integrin, alpha 10 2QQ AF112345 Hs.158237 4.2 210821096375
419341 ESTs, Weakly similar to ALU1_HUMAN ALU N71463 Hs.118888 4.2 13315814
418407 nuclear transcription factor Y, beta AL044818 Hs.84928 4.2 12375741
435520 HNOEL-iso protein AA297990 Hs.9315 4.2 31307146
409877 zinc finger protein 106 AW502498 Hs.15220 4.2 3945086 435523 membrane-spanning 4-domains, subfamily T62849 Hs.11090 4.2 31317147
449077 ESTs AW262836 Hs.252844 4.2 40637947
411666 neurofilament3 (150kD medium) AF106564 Hs.71346 4.2 5465201
410011 PFTAIRE protein kinase 1 AB020641 Hs.57856 4.2 4064075096
435370 ESTs AI964074 Hs.225838 4.2 31207136 421917 KIAA1020 protein AB028943 Hs.109445 4.2 161216136021
435818 ESTs AA700553 4.2 31547163
452110 Homo sapiens cDNA FLJ11309 fis, clone P T47667 Hs.28005 4.2 42908132
421458 carbohydrate (keratan sulfate Gal-6) su NM_003654 Hs.104576 4.2 154315445972
410286 DKFZP586N2124 protein AI739159 Hs.61898 4.2 4485125 417358 KIAA0094 protein D42084 Hs.82007 4.2 110211035641
427239 ubiquitin carrier protein BE270447 Hs.356512 4.2 23116515
407140 ESTs, Weakly similarto I38022 hypothet AA059106 Hs.271780 4.2 1154867
406923 gb:G1 phase-specific gene {3' region} [ S70622 4.2 81824844
434629 glioma-amplified sequence-41 AA789081 Hs.4029 4.2 30647090 446238 SCO (cytochrome oxidase deficient, yeas T95143 Hs.14511 4.2 38297756
433047 methionine-tRNA synthetase M86135 Hs.279946 4.2 29316983
445413 CGI-147 protein AA151342 Hs.12677 4.2 37657704
425428 DKFZP586B0621 protein AL110261 Hs.157211 4.2 210421056372
419911 BN51 (BHK21 ) temperature sensitivity co L15301 Hs.1276 4.2 139313945861 436856 ESTs AI469355 Hs.127310 4.2 32207221
411529 Homo sapiens cDNA FLJ12927 fis, clone N AA430348' Hs.28229 4.1 5395196
417259 chondroitin sulfate proteoglycan 2 (ver AW903838 Hs.81800 4.1 10925632
451489 amyloid beta (A4) precursor protein-bin NM 005503 Hs.26468 4.1 423342348088
450300 ESTs, Highly similar to ITH4_HUMAN INTE AL041440 Hs.58210 4.1 41548024 425688 NGFI-A binding protein 2 (ERG1 binding U48361 Hs.159223 4.1 212421256386
424066 ESTs, Weakly similar to I38022 hypothet Z99348 Hs.112461 4.1 18916223
440129 ESTs, Weakly similar to S71886 Ste20-li AA865818 Hs.369523 4.1 34567436
417115 small nuclear ribonucleoprotein polypep AW952792 Hs.334612 4.1 10815622
453922 budding uninhibited by benzimidazoles 1 AF053306 Hs.36708 4.1 446744688279 429005 lymphocyte antigen 95 (activating NK-re AJ225109 Hs.194721 4.1 249925006662
439755 B7 homolog 3 AW748482 Hs.77873 4.1 34307413
434608 hypothetical protein FLJ22995 AA805443 Hs.179909 4.1 30637089
424378 neural cell adhesion molecule 1 W28020 Hs.167988 4.1 19406257
410813 gb: QV4-N N0039-040500-196-g04 NN0039 Horn AW895909 4.1 4965160 435538 low density lipoprotein receptor-relate AB011540 Hs.4930 4.1 313231337148
446444 ESTs AI743737 Hs.24370 4.1 38387764
437789 ESTs, Weakly similar to T17330 hypothet AI581344 Hs.127812 4.1 32877280
412677 ESTs AW029608 Hs.17384 4.1 6295267
453833 cytochrome P450, subfamily VIIIB (stero AF090320 Hs.35718 4.1 444644478264 414591 ESTs, Weakly similar to ALU8_HUMAN ALU AI888490 Hs.248107 4.1 8345435
421686 KIAA0584 protein AB011156 Hs.106794 4.1 157815795993
422737 collagen, type 111, alpha 1 (Ehlers-Dan M26939 Hs.119571 4.1 173017316108
429317 Homo sapiens cDNA: FLJ21243 fis, clone AA831552 Hs.268016 4.1 25446696
428134 ESTs AA421773 Hs.161008 4.1 24016586 419625 nuclear factor of kappa light polypepti U91616 Hs.182885 4.1 136213635836
450835 hypothetical protein FLJ10767 BE262773 Hs.25584 4.1 41998060
444901 ESTs AA357543 Hs.250829 4.1 37327678
409585 mitochondrial ribosomal protein L2 R62410 Hs.55041 4.1 3635062
445730 ESTs AI624342 Hs.179082 4.1 37957726 413125 glyoxalase I BE244589 Hs.75207 4.1 6825313
437786 polymerase (DNA directed), eta BE142681 Hs.155573 4.0 32867279
448719 trinucleotide repeat containing 3 AA033627 Hs.21858 4.0 40287920
411704 hypothetical protein FLJ10074 AI499220 Hs.71573 4.0 5475202
430287 ESTs, Weakly similar to LEU5_HUMAN LEUK AW182459 Hs.125759 4.0 26766790 426075 ESTs, Weakly similar to 2109260A B cell AW513691 Hs.270149 4.0 21706417
411263 kinesin-like 6 (mitotic centromere-asso BE297802 Hs.69360 4.0 5235182
439092 gb:oc44f08.s1 NCI_CGAP_GCB1 Homo sapien AA 830149 4.0 33767359
443957 hypothetical protein FLJ23412 AA521049 Hs.353013 4.0 36627622
429150 s oothened (Drosophila) homolog AF120103 Hs.197366 4.0 251925206677 444412 Homo sapiens clone HH409 unknown mRNA AI147652 Hs.216381 4.0 37007655
429290 neurofilament, heavy polypeptide (200kD AF203032 Hs.198760 4.0 253825396692
432335 ESTs AA534039 Hs.377990 4.0 28666929
409132 protein kinase, AMP-activated, beta 2 n AJ224538 Hs.50732 4.0 3093105025
423880 DKFZP564C186 protein BE278111 Hs.134200 4.0 18616203 452097 a disintegrin-like and metalloprotease AB002364 Hs.27916 4.0 428742888130
407137 gb:ye53h05.s1 Soares fetal liver spleen T97307 4.0 1144866 419690 Homo sapiens CDNA FLJ11223 fis, clone P AK002085 Hs 92308 4 0 1370 5843
429134 ESTs AA446953 Hs 99004 4 0 2514 6673
430130 Homo sapiens mRNA, cDNA DKFZp761G02121 AL137311 Hs 234074 40 26502651 6772
428839 Homo sapiens CDNA FLJ14814 fis, clone N AI767756 Hs 82302 4 0 2480 6648
447924 ESTs?Weakly similar to T23110 hypothet AI817226 Hs 313413 4 0 3967 7869
436637 ESTs AI783629 Hs 26766 40 3206 7208
442328 ESTs, Weakly similar to ALU4JHUMAN ALU A1952430 Hs 150614 4 0 3556 7528
TABLE 1B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
426413 3724681 AW954494AA377823 BG219617 BG195685 BG616269AI022688
452471 31447691 AI903332 AI903301 AI903476 A1903379 AI903351 AI903262 AI903258
454090 5798941 AW062465 AW062462 BF333918 AW1 6554 AW062482 AW062481 AW062468 AW062467
435818 1361481 AA700553 A1241378 AI247835
410813 3532251 AW895702 BG003544 BG003539 BF994824 BF986640 AW895909 AW805882 A 805813 AW805808 BE176767 BI049482 BI064061
AW895888
439092 9196401 AW978407 AA830149 M85983 AW503637 BF352096
TABLE 1C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers "Dunham I et al " refere to the publication entitled
"The DNA sequence of human chromosome 2 " Dunham I et al , Nature (1999) 402489-495
Strand Indicates DNA strand from which exons were predicted Nt_posιtιon Indicates nucleotide positions of predicted exons
Pkey Ret Strand Nt_posιtιon
403088 8954241 Plus 169894-170193,170504-170806
404977 3738341 Minus 43081-43229
405704 4204244 Plus 138842-139051
403071 8954241 Plus 136688-137096
405946 6758796 Plus 28296-28830
403074 8954241 Plus 143375-143561
402408 9796239 Minus 110326-110491
403285 7230870 Minus 73908-74168,74914-75174,75295-75555
402672 8077089 Minus 65791-66596
403903 7710671 Minus 101165-102597
404567 7249169 Minus 101320101501
404561 9795980 Minus 69039-70100
405452 7656638 Minus 93876-94275
TABLE 2A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of dermatofibrosarcoma protuberans AIs divided by the 95th percentile of normal tissue AIs, where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID#
419875 proeπkephalin AA853410 Hs 93557 104 13915859
449048 similar to S68401 (cattle) glucose mdu Z45051 Hs 22920 93 40617945
441134 cellular retinoic acid-binding protein W29092 Hs 346950 87 35007475
439979 hypothetical protein FU10430 AW600291 Hs 6823 85 34427424
424326 ADAM-like disintegnn protease, decysin NM_014479 Hs 1 45296 76 193419356252
421920 gamma aminobutync acid (GABA) receptor BE551245 Hs 1438 60 16146022
423236 keratocan NM J07035 Hs 1 25750 59 178817896150
441636 Homo sapiens mRNA cDNA DKFZp566E183 (f AA081846 Hs 7921 55 35307502
420931 small inducible cytokine B subfamily (C AF044197 Hs 100431 51 149314945935
420376 protocadheπn 18 AL137471 Hs 97266 50 144714485903
426027 platelet derived growth factor beta pol NMJ02608 Hs 1 976 48 216121626411
428405 cholmergic receptor, nicotmic, alpha Y00762 Hs 2266 47 243624376615
450375 a disintegnn and metalloproteinase dom AA009647 Hs 352537 47 41598028
414085 aldehyde dehydrogenase 1 family, member AA114016 Hs 75746 46 7755384
413566 sprouty (Drosophila) homolog 4 AW604451 Hs 381153 46 7305347
453033 KIAA0281 gene product AA325869 Hs 31463 46 43838210
417153 collagen, type II, alpha 1 (pπmary ost X57010 Hs 81343 46 108410855625
440151 gb ak38e07 s1 Soares_testιs_NHT Homo sa AA868167 46 34577437
413199 ELAV (embryonic lethal, abnormal vision M62843 Hs 75236 44 6876885317
409698 short stature homeobox 2 AF022654 Hs 55967 43 3783795074
426300 delta like homolog (Drosophila) U15979 Hs 169228 43 219621976437
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 43 11625685
451698 endolhelin converting enzyme like 1 Y16187 Hs 26880 42 424942508100
434747 ESTs AA837085 Hs 372254 41 30737097
430896 spinal cord-derived growth factor-B AW968905 Hs 112885 41 27396833
424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs 93135 40 19076235
418007 matrix metalloproteinase 1 (interstitia M13509 Hs 83169 39 117711785697 429500 hexabrachion (tenascin C, cytotactin) X78565 Hs 289114 39 257425756718 412755 ESTs, Weaklysimilarto P4HA_HUMAN PROL BE144306 Hs 17989139 637 5274 421458 carbohydrate (keratan sulfate Gal-6) su NM_003654 Hs 104576 39 1543 15445972 426287 calpain 6 AF029232 Hs 169172 38 219421956436 425256 collapsin response mediator protein 1 BE297611 Hs 155392 38 2074 6352 453331 ESTs AI240665 Hs352537 38 4413 8236 416658 fϊbπllin 2 (congenital contractural ar U03272 Hs 79432 37 1020 1021 5577 425071 deiodinase, lodothyronme, type II NM 013989 Hs 1 54424 37 204320446330 418113 SRY (sex determining region Y)-box 4 AI272141 Hs 83484 37 1194 5711 415989 ESTs AI267700 Hs 351201 37 962 5530 421566 early growth response 2 (Krox-20 (Droso NMJ00399 Hs 1 395 36 1563 15645984 426457 chimenn (chimaenn) 1 AW894667 Hs 380138 36 2229 6459 448731 ESTs AI522273 Hs 173179 36 4030 7922 411852 ESTs, Weakly similar to T00329 hypothet AA528140 Hs 107515 36 555 5208 447033 Predicted gene Eos cloned, secreted w/ AI357412 Hs 157601 36 3885 7802 406687 matnx metalloproteinase 11 (stromelysi M31126 Hs 352054 36 49504823 454071 ESTs AI041793 Hs 42502 36 4487 8295 452944 ESTs AI266750 Hs 135261 36 4371 8199 447584 ESTs, Weakly similar to A53531 oncofeta W48664 Hs 263561 35 3940 7847 408938 ESTs AA059013 Hs 22607 35 279 5002 446544 ESTs, Weakly similar to Unknown [H sapi AI631932 Hs 7047 35 3855 7776 454755 gb CM1-ST0283 071299 061-h03 ST0283 Horn AW819204 35 4503 8309 449595 ESTs AW293799 Hs 255238 35 4098 7979 429139 E ESSTTss FF0099009922 Hs 66087 34 2517 6675 433645 E ESSTTss,, MMooddeerraatteellyy ssiimmiillaarr ttoo AALLUU66_HHUUMMAANN AAI1882211774466 Hs 190258 34 2995 7033 452888 eepphhnnnn BB22 AAWW995555445544 Hs 30942 34 4366 8195 439783 hhyyppootthheettiiccaall pprrootteeiinn FFLLJJ1144559944 AAII112255776600 Hs 24835 34 3431 7414 420067 H Hoommoo ssaappiieennss mmRRNNAA,, ccDDNNAA DDKKFFZZpp55664400222222 ((ff TT55224433 111 Hs 94795 34 1414 5876 414821 Fc fragment of IgG, high affinity la r M63835 Hs 77424 34 8768775465 404145 ENSP00000229781* CDNA FLJ12078 fis do 34 4738 425262 GS3955 protein D87119 Hs 155418 34 207620776354 456967 T-box 2 AW004056 Hs 168357 34 4535 8337 420173 ESTs AA256151 Hs 22999 34 1426 5886 421785 Homo sapiens cDNA FLJ11946 fis, clone H T11937 Hs 323231 33 1593 6005 416539 epithelial membrane protein 1 Y07909 Hs 79368 33 1010 1011 5570 429922 H1 histone family, member 0 Z97630 Hs 226117 33 2621 26226750 429524 KIAA1211 protein AB033037 Hs 205293 33 257725786720 414467 copine II AW903820 Hs 85752 33 821 5424 453960 ESTs N62791 Hs 231883 33 4475 8285 417333 bromodomaiπ and PHD finger containing AL157545 Hs 173179 33 1096 5636 428865 BarH-like homeobox 1 BE544095 Hs 164960 33 2485 6651 425065 Homo sapiens, clone IMAGE 3603836, mRNA AA371906 Hs 294151 33 2042 6329 435793 KIAA1313 protein AB037734 Hs 4993 32 3152 31537162 408762 ESTs BE395364 Hs 118032 32 255 4984 448719 tπnucleotide repeat containing 3 AA033627 Hs 21858 32 4028 7920 452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 32 43104311 8150 424498 hypothetical protein DKFZp761L0424 AB033043 Hs 149377 32 1963 19646274 407785 ESTs, Weakly similar to A43932 mucin 2 AW207285 Hs 98279 3 1 160 4904 408934 ESTs AI268324 Hs 146050 3 1 278 5001 435370 ESTs AI964074 Hs 225838 31 3120 7136 431089 ESTs, Weakly similar to unknown protein BE041395 Hs 374629 31 2745 6838 426991 Homo sapiens cDNA FLJ10674fis, clone N AK001536 Hs 214410 3 1 2294 6502 414175 hypothetical protein DKFZp761 D112 AI308876 Hs 103849 31 786 5394 424287 hypothetical protein DKFZp434F2322 AL133105 Hs 144633 3 1 1929 19306248 429262 spinal cord-derived growth factor-B AW503454 Hs 112885 3 1 2536 6690 416932 ESTs N20884 Hs 269039 3 1 1049 5598 417689 KIAA0128 protein, septin 2 AA828347 Hs 90998 3 1 1148 5673 408915 heptacellular carcinoma novel gβne-3 pr NMJ16651 Hs 48950 3 1 2742754998 423401 coagulation factor II (thrombin) recept NM 001992 Hs 1 28087 30 1803 18046160 400419 Target AF084545 30 22234626 447471 sprouty (Drosophila) homolog 2 AF039843 Hs 18676 30 39303931 7839 438960 ESTs H26514 Hs 167506 30 3370 7353 446259 hypothetical protein FLJ13391 AA425204 Hs 334721 30 3831 7758 428305 cartilage linking protein 1 AA446628 Hs 2799 30 2426 6607 421268 ESTs AI126821 Hs 193513 3 0 1522 5958 429006 hypothetical protein FLJ13842 AA443143 Hs 50929 30 2501 6663 432994 ESTs AA573452 Hs 150941 30 2922 6976 443709 ESTs AI082692 Hs 134662 30 3637 7600 421666 endolhelin 3 AL035250 Hs 1408 30 1574 15755991 418054 lysyl oxidase-like 2 .002318 Hs 83354 29 1184 1185 5702 413474 Homo sapiens cDNA FLJ14438 fis, clone H T86312 Hs 334485 29 726 5343 401973 NM_018896* Homo sapiens calcium channel 29 4671 449885 ESTs, Weakly similar to JC2025 hexokιnaAl673121 Hs 161610 29 4119 7997 451598 ESTs N29102 Hs 79658 29 4241 8093 412453 ESTs R20205 Hs 75236 29 589 5237 449677 gb zh85d01 s1 Soares_fetalJιver_spleen AA002071 29 4105 7985 414482 endothelm receptor type A S57498 Hs 76252 2 9 8248255426 423778 flavin containing monooxygenase 2 Y09267 Hs 132821 29 1846 18476193 400920 NM_025208* Homo sapiens spinal cord der 2 9 4640 448672 ESTs AI955511 Hs 89582 29 4025 7917 457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 29 4561 8359 451195 mesenchyme homeo box 1 U10492 Hs 438 29 421842198077 415773 ESTs, Moderately similar to A47582 B ce R21651 Hs 324725 29 947 5519 422674 ESTs, Weakly similar to JW0079 heteroge AI498100 Hs 103512 29 1724 6103 405889 ENSP00000240003* HYPOTHETICAL 373 kDa 29 4797 439130 ESTs AA306090 Hs 345588 29 3378 7361 429492 ESTs W21183 Hs 13205 29 2572 6716 422222 hypothetical protein DKFZp434A171 AI699372 Hs 374343 29 1661 6056 417675 similar to murine leucine-πch repeat p AI808607 Hs 3781 29 1144 5670 409728 ESTs AW883968 Hs 321190 29 385 5079 416083 ESTs, Weakly similar to ALU1_HUMAN ALU R53467 Hs 269122 29 971 5539 431553 cartilage linking protein 1 X78075 Hs 2799 29 2792 6874 450661 ESTs AW952160 Hs 270753 28 4178 8043 421912 Homo sapiens clone 24775 mRNA sequence AW021968 Hs 109438 28 1610 6019 429327 prostaglandin E receptor 4 (subtype EP4 AA283981 Hs 199248 2546 6698 445016 reelm U79716 Hs 12246 373837397684 428981 ESTs, Weakly similar to ALU2_HUMAN ALU BE313077 Hs 93135 2497 6660 425525 ESTs AA358883 Hs 23871 2111 6377 448493 ESTs AI524124 Hs 270307 4006 7903 419221 ESTs, Weakly similar to T46428 hypothet T65460 Hs 21192 1317 5802 428626 ESTs T95297 Hs 17551 2457 6630 428392 secretory granule, πeuroendocπne prate H10233 Hs 2265 2434 6613 408988 Homo sapiens clone TUA8 Cπ-du-chat reg AL119844 Hs 49476 289 5009 456364 Homo sapiens, clone IMAGE 3163559, mRNA AA234315 Hs 58093 4520 8324 434203 hypothetical protein PR01855 BE262677 Hs 283558 3033 7066 413064 gb RC1-HT0268 280200-015 b09 HT0268 Horn BE150462 677 5309 424633 bromodomain and PHD finger containing, T71491 Hs 173179 1980 6284 452866 Homo sapiens cDNA FU21243 fis, clone R26969 Hs 268016 4361 8191 423308 Homo sapiens mRNA for KIAA1755 protein, AI365680 Hs 114085 1793 6153 411324 gb QV1-LT0036-150200 070 d 1 LT0036 Horn AW836835 525 5184 437450 Homo sapiens mRNA, cDNA DKFZp762G123 (f AL390154 Hs 26954 3265 7260 408172 phosphoglycerate mutase 2 (muscle) W02488 Hs 46039 196 4938 451090 hypothetical protein AF175409 Hs 25924 42104211 8070 439628 ESTs W81007 Hs 323780 3412 7395 411035 gb PM0 CT0263-201099 003 f06 CT0263 Horn AW854930 511 5171 430147 hairy/enhancer-of-split related with YR R60704 Hs 234434 2652 6773 429484 sema domain, immunoglobulin domain (lg) L26081 Hs 2414 256925706714 453931 ESTs AL121278 Hs 25144 4469 8280 406387 Target Exon 4805 421509 ESTs AA292223 Hs 137459 15535978 429359 matrix metalloproteinase 14 (membraπe-ι W00482 Hs 2399 25516702 403372 sirtuin (silent mating type information 4716 414959 Homo sapiens cDNA FLJ12284 fis, clone M D59968 Hs 45184 8955478 400263 Eos Control Hs 75309 4613 451669 Homo sapiens, clone IMAGE 3603836, mRNA AA349726 Hs 294151 42438095 420028 carbohydrate (N acetylglucosamine 6-0) AB014680 Hs 8786 140814095872 410910 gb MR4-ST0125021199-017-d08 ST0125 Horn A 810204 5035165 413802 ESTs, Weakly similar to S65657 alpha 1 C AW964490 Hs 255938 7445359 423680 Homo sapiens cDNA FLJ23137 fis, clone H01345 Hs 24139 18386187 423044 protocadherin 18 AA320829 Hs 97266 17726138 429187 ESTs, Weakly similar to S65657 alpha 1 C AA447648 Hs 163872 25296683 434276 leuc e zipper, putative tumor suppress AF123659 Hs 93605 303930407070 447749 ESTs T53260 Hs 8297 39597862 440168 ESTs AA868507 Hs 126141 34587438 408643 hypothetical protein FLJ21610 F06427 Hs 12727 2464976 427700 dual specificity phosphatase 6 AA262294 Hs 180383 23616554 438549 tπnucleotide repeat containing 3 BE386801 Hs 21858 33317320 417709 KIAA0247 gene product D87434 Hs 82426 114911505674 408431 Homo sapiens cDNA FLJ22536 fis, clone AI33B631 Hs 43266 2204954 440818 ESTs AI147060 Hs 146726 34877463 414359 cadheππ 11, type 2, OB cadheππ (osteo M62194 Hs 75929 8085413 436936 ESTs AL134451 Hs 197478 32277226 411789 Adlican AF245505 Hs 72157 5535545207 429194 ESTs AA447745 Hs 371421 25306684 450141 ESTs Z44619 Hs 13205 41358010 434553 hypothetical protein FLJ21687 AW514302 Hs 193170 30607086 446019 histone deacetylase 3 A1362520 Hs 302718 38107739 445102 ESTs AW204610 Hs 22270 37437688 432812 ESTs AI935412 Hs 302718 29106965 448595 KIAA0644 gene product AB014544 Hs 21572 401540167910 425717 retmoic acid receptor, beta X07282 Hs 171495 213121326390 406964 FGENES predicted novel secreted protein M21305 87884847 429709 dickkopf (Xenopus laevis) homolog 2 BE047680 Hs 211869 26076739 458422 DnaJ (Hsp40) homolog, subfamily C, memb AI344782 Hs 9683 45748371 402354 ENSP00000221785* Hypothetical 1170 kDa 4680 402636 Target Exon 4665 415046 ESTs R40018 Hs 56400 9035484 419550 KIAA0128 protein, septin 2 D50918 Hs 90998 134813495827 429973 ESTs A1423317 Hs 164680 26286756 453876 ESTs, Weakly similar to I38022 hypothet AW021748 Hs 110406 44578271 439070 ESTs AI733278 Hs 7621 33757358 409723 ESTs AW885757 Hs 257862 3845078 424153 MAGE like 2 AA451737 Hs 141496 19046233 424962 TRAM like protein NMJ12288 Hs 1 53954 203320346323 418140 microfibπllar-associated protein 2 BE613836 Hs 83551 11965713 404627 NM_001401* Homo sapiens endothelial dif 4753 446142 ESTs AI754693 Hs 145968 38207748 445252 Homo sapiens clone 23927 mRNA sequence AF052109 Hs 12473 37527695 422152 solute carrier family 30 (zinc transpor AA909249 Hs 112282 16536049 441005 Homo sapiens mRNA, cDNA DKFZp547G133 (f Z41305 Hs 303172 34937469 447253 ESTs AW250196 Hs 103512 39077822 400352 taste receptor, type 2, member7 AF227133 1381394622 433292 gb PM3-HT0344-281299-008-a12 HT0344 Hom BE154829 Hs 18236625 2968 7009 450842 ESTs AA011358 Hs 103316 25 4200 8061 424025 HomosapienscDNA FLJ23131 fis,clone AI701852 Hs 301296 25 1887 6220 420842 hypothetical protein MGC10986 AI083668 Hs 50601 25 1485 5929 426933 ESTs AA621076 Hs 179694 25 2287 6497 440974 KIAA0700 protein AW450345 Hs 13999 25 3492 7468 400608 C10001899gι|7508633|pιrl|T25392 hypoth 25 4633 404234 Target Exon 25 4741 405521 C8001409* gι|7441226|pιrl|S31212 collag 25 4786 446617 ESTs N41529 Hs 176013 25 3859 7780 436045 DKFZP564O0423 protein AB037723 Hs 5028 25 316931707176 404030 NM-015669* Homo sapiens protocadhenn b 25 4735 452734 Homo sapiens mRNA, cDNA DKFZp43401311 (AL137616 Hs 30483 25 43498181 435056 glycoprotein M6B AW023337 Hs 5422 25 31007119 403134 C2000555*gι|6330407|dbj|BAA86514 1| (A 25 4709 434891 ESTs AA814309 Hs 123583 25 30897109 417632 glycoprotein M6B R20855 Hs 379090 25 11415667 444035 ESTs AW073319 Hs 135067 25 36737632 433842 ESTs AI652156 Hs 26346 25 30097044 412792 gb IL2-HT0449-100100-033-A09 HT0449 Hom BE162129 25 6425279 401357 tumor protein D52-lιke 1 25 4650 434067 Homo sapiens cDNA FLJ14218 fis, clone N H18913 Hs 124023 25 30267059 443996 retinal degeneration B beta H17822 Hs 333212 25 36667625 409921 gb EST00009 pGEM-T library Homo sapiens AW600239 Hs 285885 25 3985089 422982 ESTs, Weakly similar to A46010 X-lin ed AA346147 Hs 43143 25 17656132 414402 gb 601172959F1 IH MGCJ7 Homo sapiens BE294186 Hs 16468025 8125416 428211 ESTs AA424211 Hs 183176 25 24076591 421483 hypothetical protein MGC11333 NMJ03388 Hs 1 04717 25 154515465973 455811 gb MRO HT0080 011099 002-b03 HT0080 Hom BE141468 25 45088314 410534 gb QV0-NN1071-280400-207 g07 NN1071 Hom AW905138 Hs 13291 25 4715142 410642 gb CMO-UM0001-010300-258-h11 UM0001 Hom AW792784 24 4845152 433430 ESTs AI863735 Hs 369982 24 29777018 419093 spinal cord derived growth factor-B AI804054 Hs 112885 24 13045792 419073 Homo sapiens cDNA FLJ12797 fis, clone N AW372170 Hs 183918 24 12965786 451820 ESTs AW058357 Hs 199248 24 42608107 428771 KIAA1069 protein AB028992 Hs 193143 24 247124726641 438944 KIAA1444 protein AA302517 Hs 92732 24 33687351 401441 Target Exon 24 4652 405523 C8001409*gι|7441226|pιr||S31212 collag 24 4788 410781 ESTs AI375672 Hs 165028 24 4955159 453174 ESTs AI633529 Hs 135238 24 43998224 451507 ESTs, Weakly similar to T31611 hypothet AW291109 Hs 332563 24 42368090 400829 C11000244 gι|11056030|ref|NP_061738 11 24 4639 408530 LUC7 (S cerevιsιae)-lιke BE143941 Hs 16803 24 2354966 438305 gb yl79c09 si Soares infant brain 1 NIB H06377 24 33157306 440209 neurexin 3 H05049 Hs 247837 24 34617440 438703 ESTs AI803373 Hs 31599 24 33487333 420547 gonadotropm-regulated testicular RNA h AF155140 Hs 98738 24 146014615912 451752 KIAA1171 protein AB032997 Hs 353087 24 425242538102 437249 hypothetical protein FLJ21347 AA432202 Hs 103147 24 32507247 422667 ESTs H25642 Hs 132821 24 17236102 420489 ESTs AA815089 Hs 193513 24 14585910 potycylhemia rubra vera 1 , cell surface AF146747 Hs 232165 24 388138827799
441544 ESTs AW300043 Hs 127137 24 35237496 409633 ESTs AW449822 Hs 55200 24 3715068 404681 C9001188* gιl12738842|ref|NP_073725 11 24 4756 420888 dihydropyπmidinase-like 4 AB006713 Hs 100058 24 148614875930 441689 ESTs AI123705 Hs 289068 24 35337505 414933 ESTs, Weakly similar to I38022 hypothet D60141 Hs 270977 24 8935476 406107 C11002500* gι|3298456|dbj|BAA315141| ( 24 4801 446509 protocadhenn 20 AF169693 Hs 132892 24 384538467769 423556 dynein, cytoplas ic, heavy polypeptide R72694 Hs 356692 24 18166170 450278 ESTs AW205234 Hs 201587 24 41518021 439873 ESTs BE159253 Hs 300638 24 34367419 441389 endocytic receptor (macrophage manπose AF134838 Hs 7835 24 351435157488 455215 ESTs AW867003 Hs 278344 24 45068312 415314 glycoprotein M6B N88802 Hs 5422 24 921 5497 450282 ESTs AA007655 Hs 93523 24 41528022 444292 ESTs AI139794 Hs 146569 24 36907646 410333 ras association (RalGDS/AF-6) domain co AL049538 Hs 62349 2.4 4514525128 438662 cleavage and polyadenylation specific f AA223599 Hs 6351 24 33457330 401929 C17001690 gι|6005701|ref]NP_009099 1| A 24 4668 422578 caudal type homeo box transcription fac AF239666 Hs 1545 24 170 17086090 433600 ESTs R42833 Hs 22232 24 29907029 424870 ESTs T15545 Hs 244624 24 20146308 431961 Homo sapiens cDNA FLJ 11300 fis, clone P AK002162 Hs 272249 24 28366905 447357 ESTs AI375922 Hs 132821 24 39177829 402687 Target Exon 24 4688 415892 ESTs, Moderately similar to JC5238 gala H08267 Hs 125979 23 9555525 443749 ESTs R38828 Hs 143463 23 36417604 427669 ESTs, Moderately similar to KIAA1200 pr AW451832 Hs 255938 23 23586552 450203 L-kynuren e/alpha aminoadipate ammotr AF097994 Hs 301528 23 414141428015 400207 Eos Control Hs 76847 23 4599 429030 gb IL2-UM0079-030300-048-F01 UM0079 Hom AW803288 23 25036665 458956 gb ht98f11 x1 NCI_CGAP_Lu24 Homo sapien BE220675 23 45878383 451962 ESTs AW078832 Hs 226806 23 42668113 434635 Homo sapiens cDNA FLJ11934fis, clone H H47794 Hs 261699 23 3065 7091 450701 hypothetical protein XPJ98151 (leucine H39960 Hs 288467 23 4183 8048 419087 hypothetical protein FLJ14594 AI671245 Hs 24835 23 1302 5790 410244 ESTs N62178 Hs 48472 23 438 5118 441469 ESTs AW451400 Hs 127019 23 3520 7493 457455 gb EST384956 MAGE resequences, MAGL Hom AW972861 23 4551 8350 440516 cadheπn 2, type 1 , N cadhenn (neurona S42303 Hs 161 23 347234737451 457085 ESTs AA412446 Hs 365809 23 4540 8341 417231 ESTs R40739 Hs 166351 23 1090 5630 409348 ESTs AI401535 Hs 146090 23 343 5048 402741 NM-.002508 Homo sapiens nidogen (eπactin 23 4689 414259 integrin, beta-like 1 (with EGF-like re W44633 Hs 301296 23 792 5400 433235 contactm 3 (plasmacytoma associated) AB040929 Hs 35089 23 296329647006 425863 Human unidentified mRNA, partial sequen U43604 Hs 159901 23 2152 6404 452036 sema domain seven thrombospoπdiπ repea NMJ03966 Hs 27621 23 427342748119 426320 transforming growth factor, beta 2 W47595 Hs 169300 23 2205 6442 420058 Homo sapiens cDNA FLJ10561 fis, clone N AK001423 Hs 94694 23 1411 5874 423782 ESTs AI472209 Hs 323117 23 1848 6194 418678 cancer/testis antigen (NY-ESO-1) NMJ01327 Hs 87225 23 1269 12705765 430060 roundabout (axon guidance receptor, Dro NMJJ02941 Hs 301198 23 264526466768 444561 c-fos induced growth factor (vascular e NM J04469 Hs 1 1392 23 370537067658 437696 hypothetical protein dJ37E165 Z83844 Hs 5790 23 3281 7274 424893 Homo sapiens cDNA FLJ13303 fis, clone OAW295112 Hs 153648 23 2020 6313 443785 basic helix-loop helix-PAS protein AW449952 Hs 190125 23 3645 7607 409041 Hypothetical protein, XP 051860 (KIAA11 AB033025 Hs 50081 23 299 300 5017 454410 gb RC3-ST0186-181099 012 c09 ST0186 Hom AW812744 23 4499 8305 456068 RGC32 protein A1677897 Hs 76640 23 4513 8318 410126 KIAA0036 gene product BE169274 Hs 167 23 424 5109 440129 ESTs, Weakly similar to S71886 Ste20 It AA865818 Hs 369523 23 3456 7436 452352 X11L binding protein 51 BE301921 Hs 324104 23 4319 8156 411642 neuroligin 1 NM J14932 Hs 7 1132 23 544545 5200 425801 gb HSC14H051 normalized infant brain cD Z43151 Hs 343666 23 2144 6397 419133 protein tyrosine phosphatase, receptor U46116 Hs 89627 23 130713085795 401961 NMJ.21626 Homo sapiens serine carboxype 23 4669 453751 Homo sapiens cDNA FLJ21238 fis, clone R36762 Hs 101282 23 44368255 425398 hypothetical protein similar to tenasci AL049689 Hs 156369 23 210121026370 443916 hypothetical protein DKFZp434C2322 AV647043 Hs 131433 23 36587619 426322 iranscobalamin I (vitamin B12 binding p J05068 Hs 2012 23 220622076443 417337 ESTs AW292905 Hs 128770 23 10985638 408015 epidermal differentiation complex prate AW136771 Hs 244349 23 1844926 430850 gb MR0 HT0165060200-006 e02 HT0165 Hom BE144152 23 27346830 408513 ESTs AW206468 Hs 103118 23 2344965 419940 ESTs AW611903 Hs 144585 23 13975864 410581 tumor endothelial marker 7 precursor AA018982 Hs 125036 23 4785146 409098 pleckstnn homology, Sec7 and coiled/co AA132672 Hs 7984 23 3035020 434741 ESTs, Weakly similar to ALU1_HUMAN ALU AI762825 Hs 270538 23 30727096 433372 hypothetical protein FLJ23132 AI625577 Hs 287727 23 29747015 445526 A kinase (PRKA) anchor protein 7 AA223447 Hs 12835 23 37797715 414110 gb 601112444F1 NIH_MGC_16 Homo sapiens BE251752 23 7765385 403574 Target Exon 23 4724 425227 ESTs H84455 Hs 40639 23 20696348 452339 ESTs R31567 Hs 97169 23 43168154 416857 FGENESH predicted TM containing protein AA188775 Hs 292453 23 10425592 425781 class I MHC-restπcted T cell associate AF001622 Hs 159523 23 214021416395 450513 ESTs N27780 Hs 374621 23 41728038 406064 Target Exon 23 4799 434269 similar to murine leucine-πch repeat p AK001991 Hs 3781 23 303730387069 412218 gb QVO-NN1020-170400-195-h02 NN1020 Hom AW901809 23 5785227 402742 NMJ02508 Homo sapiens nidogen (enactm 23 4690 433927 small nuclear protein PRAC A1557019 Hs 116467 23 30157049 434728 Homo sapiens cDNA FLJ22749 fis, clone AA644655 23 3071 7095 411893 ESTs R82845 Hs 273789 23 5585211 444649 ESTs AW207523 Hs 371001 22 37107662 413457 ESTs AW974787 Hs 114956 22 7245341 427297 Homo sapiens, clone MGC 17333, mRNA, co AW292593 Hs 334907 22 23156518 446189 ESTs H85224 Hs 214013 22 38227750 401974 NM_018896* Homo sapiens calcium channel 22 4672 424578 hypothetical protein AK001973 Hs 150890 22 197319746280 438555 Homo sapiens mRNA for FLJ00024 protein, AI222089 Hs 143878 22 33347322 452188 ESTs AI864208 Hs 176275 22 42948136 423629 Homo sapiens cDNA FLJ21909 fis, clone AW021173 Hs 18612 22 18286180 429424 thiopunne S methyltransferase BE621985 Hs 381154 22 25596707 422611 fucosyltransferase 8 (alpha (1,6)fucos AA158177 Hs 118722 22 17126094 406483 NMJW3059* Homo sapiens solute earner 22 4807 423632 gb EST32358 Embryo, 12 week I Homo sapi AA328824 Hs 188490 22 18296181 411880 gb hm30f03 x1 NCI_CGAP_Thy4 Homo sapien AW872477 22 5565209 448664 splicing factor 3a subunit 1, 120kD AI879317 Hs 334691 22 40247916 453197 ESTs, Weakly similar to ALU5JHUMAN ALU AI916269 Hs 127804 22 44028226 423337 axiπ 2 (conductin, axil) NMJ04655 Hs 1 27337 22 179617976156 408049 desmoplakiπ (DPI, DPII) AW076098 Hs 345588 22 1874929 410929 ESTs H47233 Hs 30643 22 5045166 415400 ESTs Z42803 Hs 23772 22 9255501 413059 gb RC0 HT0295-291199031-E11 HT0295 Hom BE151498 22 6755307 453041 Homo sapiens cDNA FLJ11918 fis, clone H AI680737 Hs 289068 22 43848211 452834 KIAA1688 protein AI638627 Hs 105685 22 43568187 412591 ESTs, Weakly similar to T26845 hypothet BE217736 Hs 292653 22 6145256 434997 ESTs AW975155 Hs 146014 22 3095 7114
449461 ESTs AI652043 Hs 195363 22 4090 7972
436761 ESTs AI817776 Hs 236557 22 3213 7214
429470 guanine nucleotide binding protein (G p AI878901 Hs 203862 22 2564 6711
427129 sine oculis homeobox (Drosophila) homol H29990 Hs 356340 22 2304 6510
405078 Target Exon 22 4770
404682 ortholog of mouse polydomaiπ protein 22 4757
402864 Target Exon 22 4696
407803 ESTs, Weakly similar to T42689 hypothet AW081681 Hs 269064 22 163 4907
404673 Target Exon 22 4755
444579 ESTs, Weakly similar to A56194 thrombox AH 68336 Hs 301564 22 3708 7660
424375 Homo sapiens clone 24820 mRNA sequence AF070547 Hs 146312 22 1939 6256
424442 ESTs, Weakly similar to ZN91_HUMAN ZINC AW051949 Hs 90035 22 1954 6268
441746 ESTs H59955 Hs 127829 22 3535 7507
404735 cofilin 1 (non muscle) 22 4760
408604 ESTs D51408 Hs 21925 22 243 4973
447623 Homo sapiens cDNA FLJ23020 fis, clone AA350235 Hs 6127 22 3942 7849
431285 ESTs AW301205 Hs 189422 22 2770 6856
401851 NM 002401* Homo sapiens mitogen-activat 22 4666
419157 ESTs AA234540 Hs 23871 22 1313 5798
439696 ESTs W95298 Hs 171882 22 3419 7402
446645 ESTs AI336596 Hs 97266 22 3864 7785
438552 type I transmembrane receptor (seizure- AJ245820 Hs 6314 22 333233337321
445363 tubulm specific chaperone d NM_005993 Hs 1 2570 22 376237637702
421680 Human DNA sequence from clone CTA-984G1 AL031186 Hs 289106 22 1576 15775992
414701 gb HTM1-811F HTM1 Homo sapiens cDNA, mR BE440040 Hs 19363222 851 5447
400504 Target Exon 22 4629
407438 gb Homo sapiens candidate taste recepto AF227133 22 138 1394886
412148 gb yp82c03 s1 Soares fetal liver spleen R83307 22 574 5224
453872 ESTs R59989 Hs 176539 22 4455 8269
442204 ESTs AI635450 Hs 21914 22 3553 7525
411027 leukocyte immuπoglobulin-like receptor, AF072099 Hs 67846 22 5095105170
437230 ESTs AL133065 Hs 48996 22 3248 7245
400632 C10001871* gι|1705533|sp|P32018|CA1E_CH 22 4635
409549 phospholipase C, epsilon 2 AB029015 Hs 54886 22 3573585059
405522 C8001409* gι|7441226|pιr||S31212 collag 22 4787 \
425247 matrix metalloproteinase 11 (stromelysi NM_005940 Hs 1 55324 22 20722073 6351
416031 ESTs, Weakly similarto T00329 hypothet T30290 Hs 107515 22 963 5531
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 22 1669 16706062
425856 hypothetical protein FLJ13993 AA364908 Hs 98927 21 2151 6403
405401 C12001565* gι|11067002|gb|AAG02570 1| ( 21 4780
419049 ESTs AI278445 Hs 43334 2 1 1292 5783
406796 nbosomal protein L6 AI890167 Hs 349961 2 1 66 4833
419584 F-box only protein 24 AF053356 Hs 283764 2 1 1357 1358 5832
409672 ESTs AW971226 Hs 298893 21 375 5072
431189 ESTs AI627353 Hs 126120 21 2758 6846
455813 gb QV2-HT0083-071299 018-a11 HT0083 Hom BE141577 2 1 4509 8315
450530 cytochrome P450, subfamily 46 (choleste NM 006668 Hs 25121 2 1 417341748039
456600 DKFZP564O0823 protein AL080121 Hs 105460 21 452445258328
446904 DKFZP434H204 protein AL110226 Hs 16441 21 3875 38767795
423956 Homo sapiens clone 25215 mRNA sequence, W28203 \Hs 136169 21 1877 6214
449773 ESTs R76294 Hs 302383 2 1 4113 7991
457740 KIAA0460 protein AW500458 Hs 29956 21 4560 8358
437219 ESTs AW975966 Hs 27788 21 3246 7243
453983 ESTs H94997 Hs 16450 21 4476 8286
423944 phosphodiesterase 10A T91433 Hs 348762 21 1876 6213
405563 ENSP00000248912* IG lambda chain V regi 2 1 4790
404033 C5000413* gι|202800|gb|AAA40703 1| (M64 21 4736
423225 Thy-1 cell surface antigen AA852604 Hs 125359 21 1786 6148
457458 ESTs AW972881 Hs 276507 2 1 4552 8352
436315 hypothetical protein MGC4837 BE390513 Hs 27935 2 1 3182 7187
438393 Homo sapiens cDNA FLJ22272 fis, clone AA351815 Hs 50740 21 3319 7309
449625 odz (odd Oz/ten m, Drosophila) homolog NMJD14253 Hs 349094 21 4101 41027982
448390 hypothetical protein AL035414 Hs 21068 2 1 3999 7897
456549 ESTs AA283740 Hs 89211 2 1 4523 8327
419694 hypothetical protein FLJ22029 AW293506 Hs 285243 2 1 1372 5845
426659 ESTs, Weakly similar to T21371 hypothet AA382928 Hs 16450 2 1 2260 6478
401628 ENSP00000219101*WWP2 21 4657
430444 ESTs AW296421 Hs 121035 2 1 2700 6806
424911 ESTs AA984364 Hs 7913 2 1 2026 6317
422810 Ksp37 protein AA317400 Hs 98785 2 1 1743 6116
458935 CDP-diacylglycerol synthase (phosphatid Y16521 Hs 24812 21 458545868382
459487 gb zι78b05 s1 Soares fetal liver spleen AA699665 21 4593 8389
447771 ESTs BE505004 Hs 25348 2 1 3963 7865
436748 collagen, type VI, alpha 2 BE159107 Hs 159263 21 3212 7213
433417 Homo sapiens, Similar to RIKEN cDNA 683 AA587773 Hs 8859 21 2976 7017
411101 gb RC2-CT0298-300100014-h09 CT0298 Hom AW856816 21 514 5174
408953 ESTs AW297144 Hs 335802 2 1 282 5004
457067 hypothetical protein FLJ22624 R36022 Hs 179566 21 4539 8340
441405 ESTs AW136087 Hs 126896 21 3517 7490
400360 Homo sapiens pregnancy-induced hyperten AF232216 2 1 16 174623
435384 gb ac29b10 s1 Stratagene ovary (937217) AA679202 Hs 380314 2 1 3122 7138
442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 21 3551 7523
422766 heparan sulfate (glucosamine) 3-O-sulfo AA334108 Hs 159572 2 1 1735 6111
406904 gb Human SEF2-1 D protein (SEF2-1D) mRNA M74720 2 1 75764841
418383 ESTs AA218986 Hs 118854 21 1224 5733 401583 Target Exon 21 4655
402236 NM 025040 Homo sapiens hypothetical pro 21 4675
423604 ESTs AA486585 Hs 258901 21 1825 6178
402888 Target Exon 21 4698
443620 ESTs, Weakly similar to ALU7_HUMAN ALU AI079575 Hs 134540 2 1 3630 7593
428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs 337534 2 1 2393 6579
419198 ESTs AA234938 Hs 87384 2 1 1315 5800
446918 KIAA1577 protein AL135125 Hs 13913 21 3877 7796
447720 ESTs AL038765 Hs 161304 21 3952 7858
440483 ESTs AI200836 Hs 356890 21 3467 7446
416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 21 1001 10025564
448997 hypothetical protein FLJ20898 AA130390 Hs 25549 21 4057 7941
425403 Human DNA sequence from clone 1198H6 on AL023753 Hs 156406 21 2103 6371
457646 ESTs AA725650 Hs 112948 21 4559 8357
413482 ESTs AA129869 Hs 197143 21 727 5344
427778 ESTs AA412323 Hs 105323 21 2368 6559
419043 etsvaπantgene l T19167 Hs 89566 21 1291 5782
421568 ESTs W85858 Hs 99804 2 1 1565 5985
421398 vav 2 oncogene AW629852 Hs 4248 21 1540 5970
424551 KIAA0320 protein AB002318 Hs 150443 21 1970 1971 6278
401754 C17002014* gι|12740832|ref|XP 0086422| 21 4659
405230 C2001066 gι|10257425|ref|NP_033892 1| C 2 1 4773
419700 galactokinase 1 AF084935 Hs 92357 2 1 1373 13745846
400135 Eos Control Hs 118890 2 1 4597
408209 ets variant gene 5 (ets-related molecul NMJ04454 Hs 43697 21 2042054944
404685 NM_022127 Homo sapiens solute carrier f 21 4758
454013 growth hormone releasing hormone L00137 Hs 37023 21 44794480 8289
446048 KIAA1811 protein AI272364 Hs 182081 2 1 3815 7743
433323 ESTs AA805132 Hs 159142 2 1 2970 7011
436773 PC4 and SFRS1 interacting protein 1 AW078629 Hs 351305 21 3215 7216
415345 gb HSC11 C121 normalized infant brain cD F06228 21 924 5500
452997 ESTs N64777 Hs 44656 21 4377 8205
423582 Homo sapιens cDNA FLJ11812 fis, cloπe H BE000831 Hs 23837 2 1 1821 6174
423508 hepatitis A virus cellular receptor 1 AW604297 Hs 129711 2 1 1814 6168
437544 EST AL037786 Hs 210786 21 3269 7263
448211 PRO0659 protein BE384592 Hs 6451 21 3989 7888
421100 Homo sapiens cDNA FLJ21763 fis, clone AW351839 Hs 124660 2 1 1505 5944
414611 Homo sapiens cDNA FLJ13656 fis, clone P AA149955 Hs 85077 2 1 837 5437
400098 Eos Control 2 1 4596
414443 platelet-derived growth factor receptor AU077268 Hs 76144 21 817 5421
429091 ESTs AA935658 Hs 374241 21 2512 6671
410295 nidogen (enactin) AA741357 Hs 356624 2 1 450 5127
435397 ESTs AI809920 Hs 199676 2 1 3123 7139
430228 ESTs, Highly similar to T00391 hypothet AW950939 Hs 6382 21 2663 6780
451302 ESTs H39006 21 4223 8080
414633 gb zl07b07 s1 Soares pregnant uterus Nb AA150238 2 1 839 5439
450408 ESTs AI694959 Hs 202340 2 1 4164 8032
452328 ESTs AA805679 Hs 61271 21 4315 8153
421197 gb ∑t21 g02 r1 Soares ovary tumor NbHOT AA284739 Hs 344806 21 1516 5953
438816 gb PM0-LT0017-031299-001-C07 LT0017 Hom AW835829 21 3354 7338
439791 ESTs H77774 Hs 35755 2 1 3432 7415
440326 ESTs AW630250 Hs 132161 21 3466 7445
458846 ESTs AI589615 Hs 185602 21 4582 8379
403433 NM 001622 Homo sapiens alpha-2-HS glyco 21 4720
426773 KIAA0440 protein NMJJ15556 Hs 1 72180 21 226922706484
404917 Target Exon 21 4764
417272 ESTs AA343751 Hs 85992 21 1093 5633
428433 ESTs AA521410 Hs 41371 21 2442 6620
449634 ESTs AI656553 Hs 197715 20 4103 7983
434241 Homo sapiens PRO3077 mRNA, complete eds AF119913 20 303430357067
402001 Target Exon 20 4673
427876 ESTs AI494291 Hs 369171 20 2381 6569
409112 quinone oxidoreductase homolog BE243971 Hs 50649 20 306 5022
445289 ESTs AW275575 Hs 371247 20 3756 7698
408870 ESTs AA058586 Hs 129907 20 271 4996
419536 gb np12d11 s1 NCI CGAP_Pr3 Homo sapiens AA603305 20 1347 5826
413305 Homo sapiens cDNA FLJ23176 fis, clone NM 000426 Hs 75279 20 6976985324
455046 gb PM0 CT0237-141099 001-c0δ CT0237 Hom AW852480 20 4504 8310
424291 ephnn B1 AL120051 Hs 144700 20 1931 6249
440966 ESTs, Weakly similar to MCATJHUMAN MITO AI4O1006 Hs 376694 20 3491 7467
423469 DKFZP586N1922 protein AA326213 Hs 7357 20 1811 6166
402945 Target Exon 20 4699
419687 ESTs, Weakly similar to T2D3_HUMAN TRAN A1638859 Hs 227699 20 1369 5842
405651 Target Exon 20 4791
423925 Human clone 23629 mRNA sequence AW003668 Hs 135587 20 1873 6211
429955 ESTs, Weakly similarto ZN91_HUMAN ZINC AA461317 Hs 247150 20 2625 6753
426514 bone morphogenetic protein 7 (osteogeni BE616633 Hs 170195 20 2246 6470
448019 ESTs, Moderately similar to I38022 hypo AW947164 Hs 195641 20 3970 7872
412902 gb QV0-BN0147-290400 214-c01 BN0147 Hom BE008018 20 654 5289
427400 hypothetical protein FLJ11939 AW245084 Hs 94229 20 2325 6525
423648 hypothetical protein FLJ20449 AK000456 Hs 130546 20 1833 18346184
450785 Homo sapiens alpha-1 (VI) collagen AA852713 Hs 108885 20 4193 8056
420743 ESTs AA279885 Hs 99745 20 1475 5921
449851 ESTs AW207738 Hs 231946 20 4118 7996
419437 neogeπin (chicken) homolog 1 U61262 Hs 90408 20 1338 1339 5820
430891 G protein coupled receptor 8 U22492 Hs 248118 20 273727386832 434011 cloπe FLB5214 AW953437 Hs 5486 20 3023 7056
401972 NM_018896* Homo sapiens calcium channel 20 4670
450271 ESTs AI693900 Hs 87224 20 4150 8020
431475 putative nuclear protein AI567669 Hs 40342 20 2791 6873
406673 major histocompatibility complex, class M34996 Hs 198253 20 9091 4821
438251 ESTs AI435502 Hs 14931 20 3310 7302
402285 sclerostin 20 4677
423940 SEC14 (S cerevιsιae)-lιke 2 NM 012429 Hs 277728 20 1874 18756212
454050 ESTs AW022889 Hs 233176 20 4484 8293
428664 similar to S ALL1 (sal {Drosophιla)-lι β AK001666 Hs 189095 20 2461 6633
428878 ESTs AA436884 Hs 48926 20 2486 6652
439668 fnzzled (Drosophila) homolog 8 AI091277 Hs 302634 20 3414 7397
448882 protease, serine, 12 (neurotrypsin, mot AJ001531 Hs 22404 20 404540467933
407915 ESTs, Weakly similar to JC5256 adipocyt AI342364 Hs 313515 20 181 4923
435977 brain-specific membrane-anchored protel AL138079 Hs 5012 20 3166 7174
417563 gb zx52a10 r1 Soares fetal liver spleen AA203701 20 1133 5661
426666 CD22 antigen AW500131 Hs 171763 20 2261 6479
419200 EST AW966405 Hs 313342 20 1316 5801
415079 hypothetical protein FLJ23548 R43179 Hs 22895 20 908 5487
446205 ESTs AW172662 Hs 149479 20 3823 7751
457207 tryptophan rich basic protein i H56585 Hs 198308 20 4541 8342
442414 πbonuclease 6 precursor BE408758 Hs 8297 20 3560 7532
401356 tumor protein D52-lιke 1 20 4649
411171 gb QV2-ST0296-150200 040 c10 ST0296 Hom AW820260 20 518 5178
458202 ESTs C14215 Hs 102572 20 4568 8365
453118 ESTs AW195849 Hs 252757 20 4393 8219
445517 hypothetical protein AF208855 Hs 12830 20 377737787714
420762 doiichyl-phosphate (UDP-N-acetylglucosa U51699 Hs 143509 20 1477 5923
454074 ESTs R63503 Hs 159795 20 4488 8296
425741 Homo sapiens clone 24628 mRNA sequence AF052152 Hs 129997 20 2133 6391
442609 selenoprotein N AL020996 Hs 8518 20 3574 7544
412806 L-kynurenme/alpha-amiπoadipate amiπotr W05694 Hs 352546 20 648 5284
403226 C2001193*gιl9966829|ref|NP_065091 1| r 20 4711
434539 ESTs, Weakly similar to MUC2_HUMAN MUCI AW748078 Hs 21441020 3059 7085
427647 Homo sapiens cDNA FLJ20653 fis, clone K W19744 Hs 180059 20 2354 6548
450823 complement-d q tumor necrosis factor-re T81223 Hs 22011 20 4198 8059
446254 Homo sapiens oDNA FLJ12832 fis, clone N BE179829 Hs 179852 20 3830 7757
443888 hypothetical protein FLJ12752 AI434150 Hs 237146 20 3654 7615
444121 ESTs AI124734 Hs 40866 20 3678 7636
411536 gb 1L3 CT0219-280100-062-B11 CT0219 Hom AW850510 20 5 54410 5197
447949 EST AI446820 Hs 165839 20 3969 7871
412275 gb QV2-NN1073-220400 159 h12 NN1073 Hom AW905372 20 579 5228
456103 ESTs Z39430 Hs 213248 20 4514 8319
401111 Target Exon 20 4642
404156 C6002456 gι|6755268|ref|NP_036008 1| RA 20 4739
404293 ligand of neuronal nitric oxide synthas 20 4745
432525 ESTs, Weakly similar to YQ42 CAEEL HYPOAI796096 Hs 109414 20 2882 6943
437845 ESTs AA769578 Hs 90488 20 3290 7283
456805 empty spiracles (Drosophila) homolog 1 AW771596 Hs 140400 20 4530 8333
458560 hypothetical protein MGC16202 AI699099 Hs 246914 20 4576 8373
458676 ESTs AI692464 Hs 202263 20 4578 8375
426363 transforming growth factor, beta 3 M58524 Hs 2025 20 22102211 6446
420324 prostate androgen regulated transcnpt AF163474 Hs 96744 20 14451446 5902
406634 GDP dissociation inhibitor 1 AA386235 Hs 74576 20 31 4813
433365 ESTs AF026944 Hs 293797 20 2973 7014
422627 transforming growth factor, beta induce BE336857 Hs 118787 20 1715 6097
449579 ESTs, Weakly similar to T46425 hypothet AW207260 Hs 134014 20 4097 7978
440037 ESTs AA861611 Hs 130643 20 3447 7429
409200 KIAA0076 gene product AL042914 Hs 51039 20 325 5037
412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 20 569 5220
416110 hypothetical protein DKFZp564A176 Z42262 Hs 322844 20 974 5541
445644 ESTs, Moderately similar to A47582 B ce R77766 Hs 271593 20 3788 7720
407604 collagen, type VIII, alpha 2 AW191962 Hs 353001 20 145 4891
426919 ELAV (embryonic lethal, abnormal vision AL041228 Hs 166109 20 2284 6495
428949 hypothetical protein DKFZp434 0617 AA442153 Hs 104744 20 2490 6655
456034 gb Ul-H BI3-ala-a-12-0-Ul s1 NCI_CGAP_S AW450979 20 4510 8316
434149 hypothetical protein MGC5469 Z43829 Hs 244624 20 3030 7063
452119 ESTs AI656378 Hs 33461 20 4291 8133
447499 protocadhenn beta 16 AW262580 Hs 147674 20 3934 7842
416201 ESTs AA467752 Hs 195161 20 980 5547
423568 growth arrest-specific 2 NMJ05256 Hs 1 29818 20 1818 1819 6172
431103 pleiotrophin (hepaπn binding growth fa M57399 Hs 44 20 274827496840
433972 cisplatin resistance-associated overexp AI878910 Hs 278670 1 9 3021 7054
400235 NM 005336 Homo sapiens high density lip Hs 177516 1 9 4604
440652 ESTs AI216751 Hs 143977 1 9 3478 7456
412782 ESTs, Weakly similar to I38022 hypothet AI189211 Hs 259347 1 9 640 5277
403857 Target Exon 1 9 4730
450258 chimerm (chimaenn) 2 R94862 Hs 286055 1 9 4149 8019
431242 KIAA1201 protein AA987742 Hs 347534 1 9 2766 6853
432952 Homo sapiens cDNA FLJ12187 fis, clone M AA813887 Hs 188173 1 9 2918 6972
408212 hypothetical protein AA297567 Hs 43728 1 9 206 4945
442694 ESTs Weakly similarto T13476 hypothet AI217992 Hs 255938 1 9 3577 7547
401797 Target Exon 1 9 4663
403489 C7002058 gι|585761|sp|P38024|PUR6_CHICK 1 9 4722
452965 Human DNA sequence from clone RP11-524D A1904779 Hs 247525 1 9 4374 8202
433859 ESTs AW896758 Hs 273789 1 9 3010 7045 436252 Homo sapiens cDNA FLJ 11562 fis, clone H AI539519 Hs 142827 1 9 3179 7184
430110 gb aa24c01 r1 NCI_CGAP_GCB1 Homo sapien AA465314 1 9 2649 6771
403404 Target Exon 1 9 4718
407753 ESTs AL045916 Hs 179972 1 9 157 4901
436838 ESTs AW978101 Hs 291787 1 9 3219 7220
429150 smootheπed (Drosophila) homolog AF120103 Hs 197366 1 9 2519 25206677
420103 aldehyde dehydrogenase 1 family, member AA382259 Hs 95197 1 9 1416 5878
446936 ESTs H10207 Hs 47314 1 9 3880 7798
423961 peπostm (OSF-2os) D13666 Hs 136348 1 9 1878 18796215
440704 insulin-like growth factor binding prot M69241 Hs 162 1 9 348234837459
414764 ESTs AW013887 Hs 31522 1 9 868 5460
435931 RNA binding motif protein 9 A1077464 Hs 351478 1 9 3163 7171
426138 Homo sapiens clone 23798 and 23825 mRNA D81871 Hs 167036 1 9 2178 6423
426054 ELAV (embryonic lethal, abnormal vision U12431 Hs 166109 1 9 216421656413
427375 metallocarboxypeptidase CPX-1 AL035460 Hs 177536 1 9 23202321 6522
423600 ESTs AI633559 Hs 310359 1 8 1824 6177
420705 fetal Alzheimer antigen AB032251 Hs 99872 1 8 1471 14725919
448379 KIAA1130 protein AI097463 Hs 21035 1 8 3995 7894
431457 integrin, alpha 11 NM 012211 Hs 256297 1 8 278727886870
413195 protease, serine, 12 (neurotrypsin, mot AA127382 Hs 22404 1 8 686 5316
425064 ESTs AW953237 Hs 193513 1 8 2041 6328
411737 hypothetical protein AW160339 Hs 71791 1 8 548 5203
440293 ESTs AI004193 Hs 238889 1 8 3465 7444
434355 ESTs AA630865 Hs 186556 1 8 3049 7076
401849 Target Exon 1 8 4665
442420 ESTs AI024834 Hs 131729 1 8 3561 7533
414142 hemiceπtin (fibulin 6) AW368397 Hs 334485 1 8 781 5390
441149 ESTs AI569766 Hs 13205 1 8 3501 7476
452862 ADAMTS2 (a disintegπn-like and metall AW378065 Hs 8687 1 8 4360 8190
429910 5-hydroxytryptamιne (serotonin) recepto NMJ00867 Hs 2507 1 8 261726186747
424077 Homo sapiens mRNA, cDNA DKFZp564G1162 ( AL080082 Hs 139006 1 8 1892 6224
433455 ESTs AA360439 Hs 49476 1 8 2982 7022
437327 Homo sapiens mRNA, cDNA DKFZp761L23121 AL353942 Hs 306504 1 8 3252 7249
435908 Homo sapiens mRNA for KIAA1755 protein, AI569989 Hs 114085 1 8 3162 7170
422213 ESTs AA306385 Hs 133160 1 8 1660 6055
415910 chemokiπe (C-X3-C) receptor 1 U20350 Hs 78913 1 8 9579585527
425297 gb EST63062 Jurkat T-cells V Homo sapie AA354685 1 8 2086 6361
448425 ESTs AI500359 Hs 371249 1 8 4004 7901
410345 gb hι29d09 x1 Homo i sapien AW662559 1 8 454 5130
423013 secreted modular calcium-binding protei AW875443 Hs 22209 1 8 1769 6135
447691 sperm acrosome associated 1 AI809484 Hs 161241 1 8 3948 7855
421044 Human DNA sequence from clone RP1-238D1 AF061871 Hs 101302 1 8 1499 1500 5939
445718 ESTs H79791 Hs 15227 1 7 3794 7725
450676 ESTs AI147155 Hs 279727 1 7 4180 8045
403451 Target Exon 1 7 4721
421016 transcription factor 3 (E2A immunoglobu AA504583 Hs 101047 1 7 1497 5937
432842 hypothetical protein MGC4485 AW674093 Hs 334822 1 7 2911 6966
446782 ESTs A1653048 Hs 144006 1 7 3872 7792
412182 Splicing factor, arginine/serine-nch, AA205588 Hs 73737 1 7 577 5226
419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 1 7 1381 13825851
404394 ENSP00000241075TRRAP PROTEIN 1 7 4747
436605 ESTs AI187742 Hs 125562 1 7 3204 7206
405387 NM_022170* Homo sapiens Williams-Beuren 1 7 4779
440676 LIM and senescent cell antigen like dom NMJ04987 Hs 1 12378 1 7 347934807457
404208 C6001282 gι|4504223|ref|NP_000172 1| gl 1 7 4740
437118 CD9 partner 1 AB037857 Hs 300591 1 7 323632377235
403790 NM 001334* Homo sapiens cathepsin O (CT 1 7 4728
431467 Homo sapiens mRNA, cDNA DKFZp434E0528 ( N71831 Hs 256398 1 7 2789 6871
432439 Homo sapiens cDNA FLJ12394 fis, clone M AW972926 Hs 209209 1 7 2875 6937
405203 NM_002086* Homo sapiens growth factor r 1 7 4772
426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 1 7 2219 6453
443813 Homo sapiens mRNA, cDNA DKFZp667D095 (f AA876372 Hs 9396' I 1 7 3648 7610
440650 Human DNA sequence from PAC 75N13 on ch R4469. ! Hs 326801 1 7 3477 7455
412454 ESTs R55745 Hs 75236 1 7 590 5238
447198 ESTs D61523 Hs 283435 1 6 3898 7814
432975 chimenn (chimaeπn) 2 AA331517 Hs 286055 1 6 2920 6974
445139 synaptotagmin XIII AB037848 Hs 12365 1 6 374637477691
433212 ESTs BE218049 Hs 121820 1 6 2956 7001
442739 cytosolic acyl coenzyme A thioester hyd NM 007274 Hs 8679 1 6 3581 35827550
420208 silver (mouse homolog) like BE276055 Hs 95972 1 6 1431 5891
425841 ESTs BE262951 Hs 99052 1 6 2148 6400
404977 Insulin-like growth factor 2 (somatomed 1 6 4766
447565 chromosome 12 open reading frame AF052105 Hs 18879 1 6 3939 7846
433013 axin 2 (conductin, axil) AI697890 Hs 127337 1 6 2927 6979
425082 inositol 1,4,5 triphosphate receptor, t N44238 Hs 102991 1 6 2048 6333
448299 hypothetical protein FLJ 10392 AA497044 Hs 20887 1 6 3992 7891
432682 ESTs A1376400 Hs 159588 1 6 2896 6955
407054 gb H sapiens NOS2 gene, exon 27 X85781 1 6 101 4855
430238 hydroxyacid oxidase 2 (long chain) N72519 Hs 236545 1 6 2665 6782
421917 KIAA1020 protein AB028943 Hs 109445 1 6 1612 16136021
445537 EGF-like domain, multiple 6 AJ245671 Hs 12844 1 6 37803781 7716
421948 keratin 6A L42583 Hs 334309 1 6 1618 16196025
428418 ESTs AI368826 Hs 8768 1 6 2441 6619
405674 NM_022775 Homo sapiens hypothetical pro 1 5 4792
456629 histone deacetylase 3 AW891965 Hs 367942 1 5 4526 8329
433577 ESTs AW007080 Hs 284192 1 5 2989 7028 429686 Homo sapiens cDNA FLJ21086 fis clone AI871613 Hs 159066 1 5 2604 6736 421187 KIAA0680 gene product NMJ14721 Hs 1 02471 1 5 1514 15155952 400333 ATP7B S77447 1 5 1011 4620 415705 coi n U06632 Hs 966 1 5 9439445516 444083 gb oo17a10 x1 Soares NSF_F8 9W OT_PA_P_AI123195 Hs 47783 1 5 3674 7633 443184 ESTs AI638728 Hs 135159 1 5 3607 7574 433209 KIAA1474 protein AB040907 Hs 278436 1 4 295329546999 449969 Homo sapiens cDNA FLJ14337fis, clone P AW295142 Hs 180187 1 4 4123 8001 400220 Eos Control Hs 155560 1 4 4600 418819 ESTs AA228776 Hs 191721 1 4 12745769 425176 TEA domain family member 1 (SV40 transc AW015644 Hs 42458 1 4 20636344 417366 small proline πch protein 1 B (cornifin BE185289 Hs 1076 1 4 11045642 418154 nuclear receptor subfamily 1 , group I, BE165866 Hs 352403 1 4 11975714 433075 sortiliπ 1 NM_002959 Hs 3 51872 1 4 293629376987 451166 ESTs T98171 Hs 185675 1 4 42168075 401914 Target Exon 1 4 4667 446619 secreted phosphoprotein 1 (osteopontm, AU076643 Hs 313 1 4 38617782 430390 KIAA0969 protein AB023186 Hs 343666 1 4 268626876797 454478 superoxide dismutase 2 mitochondπal AW805749 Hs 372783 1 3 45018307 443271 ESTs BE568568 Hs 159066 1 3 36167582 428748 Ksp37 protein AW593206 Hs 98785 1 3 24686638 417258 gb yy60a09 s1 Soares_multιpIe_sclerosιs N58885 Hs 166361 1 3 10915631 403830 NM_001328* Homo sapiens C-terminal bind 1 3 4729 419301 tenomodulin protein AA236166 Hs 132957 1 3 13285811 423325 hypothetical protein FLJ22427 R55565 Hs 334691 1 3 17946154 431566 J domain containing protein 1 AF176012 Hs 260720 1 3 279727986877 432078 hypothetical protein FLJ12541 similart BE314877 Hs 24553 1 3 28386907 435886 hepatocellular carcinoma associated ant BE265839 Hs 12126 1 3 31597167 407100 gb F1 1179D 22 week old human fetal liv R29657 1 3 1084860 444015 ESTs AI472865 Hs 135534 1 3 36697628 400252 NM_004651* Homo sapiens ubiquitin speci Hs 171501 1 3 4609 422567 glypican δ AF111178 Hs 118407 1 3 170217036087 408784 ESTs AW971350 Hs 63386 1 3 2574986 431759 G protein pathway suppressor 1 U20285 Hs 268530 1 2 281828196893 439343 hypothetical protein FLJ11808 AF086161 Hs 114611 1 2 33947377 433058 Homo sapiens, Similar to CG8405 gene pr H86865 Hs 380962 1 2 29336985 422168 S100 calcium binding protein A7 (psoπa AA586894 Hs 112408 1 2 16546050 400259 NM_017432* Homo sapiens prostate tumor Hs 19555 1 2 4610 431725 Nome disease (pseudoglioma) X65724 Hs 2839 1 2 281228136888 419418 tuberous sclerosis 2 X75621 Hs 90303 1 2 133513365818 433220 ESTs AI076192 Hs 131933 29577002 428698 KIAA1866 protein AA852773 Hs 334838 24636635 401203 Target Exon 4647 420798 keratin 10 (epider olytic hyperkeratosi W93774 Hs 99936 1479 5925 431393 ESTs, Highly similar to cytokine recept AW971493 Hs 134269 2780 6864 406885 gb Human mRNA for pre mRNA splicing fac D28423 73744840 427666 calmodulin like skin protein (CLSP) A1791495 Hs 180142 2356 6550 457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs 32399 4543 8344
TABLE 2B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
440151 1879911 AA868167 F21558 F31418 F35624
454755 1070995 1 AW819203AW819204AW819197 AW819202 AW819211 BE158469 AW819221 BE158473AW819235 AW819207AW819220
AW819208 AW819238AW819198 AW819234
449677 79505 AA002232 T99209AA002071 413064 1101606J BE150469 BE150462 BE063366 BE150799 BE063378 BG952296 411324 1076104 1 AW836835AW836833 T02838 411035 352355J BF697879 BG984482 AW854930 AW854941 AW814115 AW814431 AW814190 BF325887 BF325890 BF985536 410910 1063929 AW810196 AW810555 AW810507 AW810204 AW810619 AW810534 412792 7586 19 BE162129 AW997959 455811 124024 BE141466 BE141531 BF336589 BF336571 BE141527 BF368787 BE141530 AA663234 BE141468 BE141484 410642 1044044 1 AW792784 H06639 Z44444 438305 999803 1 H06377 AW628008 429030 1058507 1 AA443446 AW803288 AW803356 BE349897AW803287 BI015966 458956 81880 1 BE873716 BE907282 AA009992 BE220675 AA345621 457455 1077062 1 AW838069 AW972861 AA523684 T05725 454410 6852 9 AW812744 AW581974 BG985054AW812725 430850 296806J BE144152 AA487799 BF916865 AA937952 414110 1634167J BE253764 BE250764 BE255757 BE251752 BE251925 412218 1159394J AW901809 AW901787AW901792AW901744 AW901753 AW901807 AW901798AW901795 434728 36765_8 AV733124 AW630740 AA644655 411880 1139083 1 BE088101 T05990 AW872477 413059 1488711_1 BE063078 BE151503 BE151498 412148 1155069 R83307AW895776AW895655 455813 1515590J BE141577 BE141585 BE141587 459487 135353 1 AA699665 R84889 411101 1232297 1 AW856816 AW856814AW817559 AW856813 AW856810 AW817561 AW861130 AW861132 AW856811 AW861135AW934798
AW817558
415345 1870623J R60302 F06228 R18381 451302 84753 1 AA017069 H39010 H39006 414633 3280746 1 AA150368 AA150238 438816 1075247 1 AW835829 R01759AA826305 434241 63414 1 AF119913 AI207698 R57074 419536 251846 1 AA244095AA603305AA244183 455046 109226ΪJ AW852480 AW852484 AW852493 412902 1476802J BE008024 BE008022 BE008026 BE008029 BE008025 BE008027 BE008020 BE008018 BE008019 BE008021 BE008015
BE008023 BE008030 BE007959 BE008016 BE008014 BE008028 BE007994
417563 2243443 AA203701 R86895 411171 1071787 1 AW820332AW820260 R94406 411536 1089425 1 AW850510 BE143820 BF349605 BE143792 412275 319144 1 BF952703 BF952683 BF952777 BF952870 BF952880 BF952714 BF947615 AW905341 AW905312 AW905371 BF952646
BF952879 AW905391 AW905372
456034 685586 1 AA136653 AA136656 AW450979 AA984358 AA809054 AW238038 AA492073 BE168945 430110 1233222 AW968358 AA46531 AA465464 AW976324 AA465465 425297 1227439J AW962101 AA354685 H85269 R55281 F11427 410345 1007452 1 AW662559 R92204 R92309 426413 372468 1 AW954494AA377823 BG219617 BG195685 BG616269 AI022688
TABLE 2C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers "Dunham I et al " refers to the publication entitled
The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
404145 9863643 Plus 30607-31266
401973 3126777 Plus 82036-82187,82950 83059,84113-84246,8453
400920 7547222 Minus 129895-130075,133882-134086
405889 7677717 Plus 53701-53825
406387 9256180 Plus 116229-116371,117512-117651
403372 9087278 Minus 130002 130131
402354 8886964 Plus 54039-54154
402636 9958122 Minus 108409-108893
404627 9796599 Plus 65191-65388
400608 9887666 Minus 96756-97558
404234 8247273 Plus 27209-27380
405521 9454643 Plus 65096-65247,77508-77637,81242-81364,8424
404030 7671252 Plus 149362-151749
403134 9211444 Plus 76642-76800
401357 9931663 Plus 143295-143425
401441 8248727 Plus 139505-139628
405523 9454643 Plus 114550-114688,117265-117407,119490-11959
400829 8570385 Plus 152176-152616
404681 9797231 Minus 40430-40549
406107 9126889 Plus 33807-33931
401929 3810670 Minus 3167-3286,4216-4310
402687 8318556 Plus 160550-160705,161161-161349
402741 9212200 Minus 18603-18760,19719-19890
401961 4581193 Minus 124054-124209
403574 8101156 Plus 5542-6176
406064 9111535 Minus 110744-111133
402742 9212200 Minus 23487-23613
401974 3126777 Plus 85330-85683
406483 7711304 Plus 49021-49147
405078 7798783 Plus 111012-111208
404682 9797231 Minus 40977-41150
402864 5881341 Plus 93475-93648,101571-101743,102803-102937,
404673 9797204 Minus 26201-26391,26768-27034,27467-27564,2865
404735 4190944 Plus 137269-138200
401851 7770425 Minus 146443-146664,147794-147971,148351-14848
400504 9796369 Minus 156301-157005
400632 3818355 Plus 72875-73447,75874-76425
405522 9454643 Plus 103664-103803,111740-111863,112064-11220
405401 6850244 Minus 5753-5866,11177-11294,12712-12817
405563 2114222 Plus 15385-15752
404033 8122195 Plus 7976-8156
401628 8575954 Minus 210617-210796
401583 9800594 Minus 22044-22120,22887-23029
402236 7690107 Plus 54636-55502
402888 9930892 Minus 54727-54901
401754 9838215 Minus 50722-50883,51021-51134,51261-51324
405230 7249032 Minus 97493-97682
404685 9797437 Minus 153217-153315,154043-154124,159185-15935
403433 9719611 Minus 72225-72437
404917 7341851 Plus 49330-49498
402001 9501818 Plus 68052-68223
402945 9368458 Minus 100591-100710
405651 4926905 Minus 80289-80357, 116604-116672, 118630-118698,
401972 3126777 Plus 67726-67849,69495-6956369690-69874,7083
402285 2689079 Minus 92386-92634
401356 9931663 Minus 110335 110442,110581-110739,111294-11146
403226 7630996 Plus 114887-115301
401111 9966191 Minus 188185-188986
404156 9886577 Plus 127319-127754
404293 3046744 Minus 85067-85654
403857 7708910 Minus 2524-3408 401797 6730720 Plus 6973-7118 403489 7331314 Minus 38897-39212 403404 9438460 Plus 22392-22598,22967-23148 401849 7770425 Plus 129375 129483,129597-129720 403451 9838240 Plus 77382-78300 404394 3135305 Minus 37121-37205,37491-37762,41053 41140,4132 405387 6587915 Minus 3769-3833,5708-5895 404208 3080468 Minus 105346-105573 403790 8084957 Minus 87826 87947,89835-90002 405203 7230116 Plus 125295-125463 404977 3738341 Minus 43081-43229 405674 4589984 Plus 68302-68429 401914 9369520 Plus 62537-62945,63155-63308 403830 9887814 Minus 20687-20893 401203 9743387 Minus 172961-173056,173868-173928
TABLE 3A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of fibrosarcoma AIs divided by the 50th percentile of normal tissue AIs, where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
428087 troponin C2, fast AA100573 Hs 182421 37 1 2396 6582
407245 titin X90568 Hs 172004 36 1 132 1334881
413778 myosin, light polypeptide 2, regulatory AA090235 Hs 75535 336 740 5356
425545 Homo sapiens, clone MGC 12401, mRNA, co N98529 Hs 158295 30 2 2114 6379
426752 Win X69490 Hs 172004 302 226622676482
409169 (clone PWHLC2-24) myosin light chain 2 F00991 Hs 50889 276 316 6029
400440 nebulm X83957 Hs 83870 246 24254627
407013 gb Human nebulm mRNA, partial eds U35637 Hs 83870 234 94 954851
422867 cartilage oligomenc matrix protein (ps L32137 Hs 1584 226 1751 17526122
428221 ATPase, Ca transporting, cardiac muscle U96781 Hs 183075 223 240824096592
412129 troponin T3, skeletal, fast M21984 Hs 73454 220 571 5725222
406704 myosin, heavy polypeptide 7, cardiac mu M21665 Hs 929 207 55564826
406707 myosin, heavy polypeptide 2, skeletal m S73B40 Hs 931 206 61 624829
412519 troponin T1, skeletal, slow AA196241 Hs 73980 184 598 5244
405001 interleukin enhancer binding factor 1 183 4767
417435 carbonic anhydrase III, muscle specific NMJ05181 Hs 82129 182 1121 11225655
418205 troponin I, skeletal, fast L21715 Hs 83760 174 120412055720
452838 preferentially expressed antigen m mel U65011 Hs 30743 170 435743588188
422633 enolase 3, (beta muscle) X56832 Hs 118804 169 1716 17176098
406706 myosin, heavy polypeptide 1 , skeletal m X03740 Hs 231581 169 59604828
422640 troponin C, slow M37984 Hs 118845 169 1718 1719 6099
410223 calsequestπn 1 (fast-twitch, skeletal S73775 Hs 60708 157 4334345115
418391 troponin I, skeletal, slow NM 03281 Hs 84673 139 122812295736
414152 thrombospondm 4 NM-.003248 Hs 75774 137 7827835391
416373 ESTs, Weakly similarto S12658 cysteine AA195845 Hs 73680 137 996 5559
417070 titin Z19077 Hs 172004 135 1070 5614
446523 sarcolipin NMJ03063 Hs 334629 134 385238537774
422069 titin cap (telethonin) AJ010063 Hs 343603 134 1635 16366037
431204 cytochrome c oxidase subunit Via polype F28841 Hs 250760 134 2760 6848 428405 cholinergic receptor, nicotinic, alpha Y00762 Hs 2266 132 243624376615 421566 early growth response 2 (Krox-20 (Droso NM_000399 Hs 1 395 129 1563 15645984 409096 sarcomeπc muscle protein AA194412 Hs 50550 128 302 5019 418533 myosin-biπdiπg protein C, fast-type NMJ04533 Hs 85937 125 1253 12545754 424982 phosphorylase, glycogen, muscle (McArdl U94777 Hs 351580 124 203620376325
431205 tropomodulm 4 (muscle) AA194560 Hs 250763 124 2761 6849 408915 heptacellular carcinoma novel gene-3 pr NM_016651 Hs 48950 123 2742754998 419138 ryanodine receptor 1 (skeletal) U48508 Hs 89631 123 130913105796
418390 titin immunoglobulin domain protein (my AF133820 Hs 84665 11 6 1226 12275735
450701 hypothetical protein XP_098151 (leucine H39960 Hs 288467 11 5 4183 8048
400499 C10001858 gι|6679124|ref|NP_032759 1| n 11 4 4628
430681 ESTs AW969675 Hs 291232 11 3 27196819
426429 myosin-binding protein C, slow-type X73114 Hs 169849 11 1 222422256456
444381 hypothetical protein BC014245 BE387335 Hs 283713 11 1 36977652
420103 aldehyde dehydrogenase 1 family, member AA382259 Hs 96197 11 1 14165878
428398 ESTs AI249368 Hs 98558 10 8 24356614
426300 delta-like homolog (Drosophila) U15979 Hs 169228 108 219621976437
420197 ESTs, Weakly similar to A57291 cytokine AW139647 Hs 88134 106 14295889
400651 ENSP00000228031* COPPER CHAPERONE FOR S 106 4636
434352 small muscle protein, X linked AF129505 Hs 86492 105 304730487075
453331 ESTs AI240665 Hs 352537 105 44138236
429973 ESTs A1423317 Hs 164680 103 26286766
411102 tnadin AA401295 Hs 23926 10 3 5155175
416658 fibπllin 2 (congenital contractural ar U03272 Hs 79432 10 1 102010215577
406687 matrix metalloproteinase 11 (stromelysi M31126 Hs 352054 10 1 49504823
437206 ESTs Weakly similar to I38344 titin, c AW975934 Hs 172004 99 32457242
416378 ankyπn repeat domain 2 (stretch respon AW044467 Hs 73708 97 9975560
436519 myozenin AJ278124 Hs 238756 97 319631977200
444329 hypothetical protein FLJ12921 W73753 Hs 209637 97 36937648 418072 Human DNA sequence from clone RP3-: J53C1 F3521C I Hs 86507 97 1190 5707
410621 titin AA194329 Hs 172004 96 481 5149
435370 ESTs AI964074 Hs 225838 95 3120 7136
419550 KIAA0128 protein, septin 2 D50918 Hs 90998 94 1348 13495827
429997 apolipoprotein B mRNA editing enzyme, C NMJ06789 Hs 227457 93 263626376761
416349 myomesin (M-protein) 2 (165kD) X69089 Hs 79227 92 991 9925556
419301 tenomodulm protein AA236166 Hs 132957 92 1328 5811
421296 penlipin NM 002666 Hs 1 03253 92 1525 15265961
441134 cellular retmoic acid-bmding protein W29092 Hs 346950 92 3500 7475
450375 a disintegnn and metalloproteinase dom AA009647 Hs 352537 91 4159 8028
409028 Z-band alternatively spliced PDZ motif AB014513 Hs 49998 86 2962975015
423961 peπostin (OSF-2os) D13666 Hs 136348 86 1878 18796215
421512 myomegalin AB007923 Hs 265848 85 155415555979
444301 asporιn (LRR class 1) AK000136 Hs 10760 85 3691 36927647
411789 Adlican AF245505 Hs 72157 85 5535545207
419050 adenosine monophosphate deaminase 1 (is NM_000036 Hs 89570 85 1293 12945784
428698 KIAA1866 protein AA852773 Hs 334838 84 2463 6635
417689 KIAA0128 protein, septin 2 AA828347 Hs 90998 83 1148 5673
425065 Homo sapiens, clone IMAGE 3603836, mRNA AA371906 Hs 294151 83 2042 6329
406964 FGENES predicted novel secreted protei ιπ 21305 82 87884847
429500 hexabrachion (tenascin C, cytotactm) X78565 Hs 289114 8 1 257425756718
443727 ESTs Z25389 Hs 18459 81 3640 7603
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 80 166916706062
414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 80 789 5397
419875 proenkephalin AA853410 Hs 93557 80 1391 5859
427674 H2B histone family, member Q NMJ03528 Hs 2 178 79 235923606553
450300 ESTs, Highly similar to ITH4 HUMAN INTE AL041440 Hs 58210 79 4154 8024
429134 ESTs AA446953 Hs 99004 79 2514 6673
418113 SRY (sex determining region Y)-box 4 AI272141 Hs 83484 79 1194 5711
415672 ESTs N53097 Hs 193579 79 937 5511
424408 collagen, type V, alpha 1 AI754813 Hs 146428 79 1943 6260
424086 lysyl oxidase AI351010 Hs 102267 78 1896 6227
424688 myosin, light polypeptide 3, alkali, ve AA216287 Hs 1815 77 1988 6290
440704 insulm-iike growth factor binding prat M69241 Hs 162 77 348234837459
411852 ESTs, Weakly similar to T00329 hypothet AA528140 Hs 107515 77 555 5208
451681 ESTs, Weakly similar to AA64JHUMAN 64 K Z28564 Hs 255950 77 4245 8097
423575 intron of peπostin (OSF-2os) C18863 Hs 163443 75 1820 6173
425308 receptor tyrosine kinase like orphan re M97639 Hs 155585 74 20872088 6362
421458 carbohydrate (keratan sulfate Gal 6) su NM.003654 Hs 1 04576 74 1543 15445972
417333 bromodomain and PHD finger containing , AL157545 Hs 173179 74 1096 5636
418156 nuclear receptor subfamily 1, group I, W17056 Hs 83623 74 1198 5715
408493 phosphoglycerate mutase 2 (muscle) BE206854 Hs 46039 73 231 4962
420212 calcium channel, voltage dependent, L t NM 000069 Hs 1 294 73 143214335892
416931 adipose most abundant gene transcript 1 D45371 Hs 80485 73 104710485597
417074 guanidinoacetate N methyltransferase Z49878 Hs 81131 73 1071 10725615
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 72 1162 5685
421552 secreted frizzled related protein 4 AF026692 Hs 105700 72 1559 15605982
448493 ESTs AI524124 Hs 270307 72 4006 7903
442376 Homo sapiens cDNA FLJ12228 fis, clone M W95588 Hs 129982 72 3557 7529
438091 nuclear receptor subfamily 1, group I, AW373062 Hs 351546 72 3302 7295
438089 nuclear receptor subfamily 1, group I, W05391 Hs 351546 71 3301 7294
449048 similar to S68401 (cattle) glucose mdu Z45051 Hs 22920 71 4061 7945
428957 WNT1 inducible signaling pathway protei NM 003881 Hs 1 94679 70 2491 24926656
427639 Homo sapiens, clone MGC 18257, mRNA, co AW444530 Hs 350860 70 2353 6547
418054 lysyl oxidase like 2 NM 002318 Hs 83354 70 1184 11855702
440042 ESTs AI073387 Hs 133898 70 3448 7430
408988 Homo sapiens clone TUA8 Cn du chat reg AL119844 Hs 49476 69 289 5009
407112 ESTs, Weakly similar to ALU7_HUMAN ALU AA070801 Hs 51615 69 111 4863
414443 platelet-derived growth factor receptor AU077268 Hs 76144 69 817 5421
425227 ESTs H84455 Hs 40639 68 2069 6348
414085 aldehyde dehydrogenase 1 family, member AA114016 Hs 75746 68 775 5384
422148 histidine-πch calcium binding protein M60052 Hs 1480 68 1651 16526048
407204 ESTs, Weakly similar to ALU1_HUMAN ALU R41933 Hs 140237 68 121 4873
441636 Homo sapiens mRNA, cDNA DKFZp566E183 (f AA081846 Hs 7921 68 3530 7502
453392 SRY (sex determining region Y) box 11 U23752 Hs 32964 68 441644178239
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 68 3057 7083
431089 ESTs, Weakly similar to unknown protein BE041395 Hs 374629 68 2745 6838
424375 Homo sapiens clone 24820 mRNA sequence AF070547 Hs 146312 68 1939 6256
451698 endothelin converting enzyme like 1 Y16187 Hs 26880 67 42494250 8100
416559 ESTs A1039195 Hs 128060 67 1012 5571
413011 biglycan AW068115 Hs 821 67 669 5302
452862 ADAMTS2 (a disintegnn like and metall AW378065 Hs 8687 67 4360 8190
420028 carbohydrate (N-acetylglucosamιne-6-O) AB014680 Hs 8786 67 1408 14095872
433577 ESTs AW007080 Hs 284192 67 2989 7028
423044 protocadhenn 18 AA320829 Hs 97266 66 1772 6138
410102 ESTs, homologue of PEM 3 [Ciona savigny AW248508 Hs 279727 66 422 5107
418045 ESTs AI972919 Hs 118837 66 1183 5701
419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 66 1381 13825851
435905 KIAA0456 protein AW997484 Hs 5003 66 3160 7168
432408 ESTs, Weakly similarto A46010 X-linked N39127 Hs 356235 65 2872 6934
439688 hypothetical protein FLJ12921 AW445181 Hs 209637 65 3418 7401
448731 ESTs AI522273 Hs 173179 65 4030 7922
421143 immunoglobulin superfamily containing I AB024536 Hs 102171 65 15101511 5949
423778 flavin containing monooxygenase 2 Y09267 Hs 132821 65 1846 18476193
429892 myomesin 1 (skelemin) (185kD) NM 003803 Hs 2504 64 261426156745
413566 sprouty (Drosophila) homolog 4 AW604451 Hs 381153 64 730 5347 453575 peplidyl arginine deiminase, type II AB023211 Hs 33455 64 44254426 8246
407656 Homo sapiens mRNA, cDNA DKFZp434B2119 AW747986 Hs 37443 64 148 4893
420376 protocadhenn 18 AL137471 Hs 97266 63 1447 14485903
411296 growth suppressor 1 BE207307 Hs 10114 63 524 5183
423225 Thy-1 cell surface antigen AA852604 Hs 125359 63 1786 6148
433235 contactin 3 (plasmacytoma associated) AB040929 Hs 35089 63 2963 29647006
421487 senne/threonine kinase 23 AF027406 Hs 104865 63 1548 15495975
402621 Target Exon 63 4684
420842 hypothetical protein MGC10986 AI083668 Hs 50601 63 1485 5929
409361 sine oculis homeobox (Drosophila) homol NMJ05982 Hs 54416 63 3443455049
431183 KDEL (Lys-Asp-Glu-Leu) eπdoplasmic reti NMJ06855 Hs 250696 63 275627576845
413199 ELAV (embryonic lethal, abnormal vision M62843 Hs 75236 62 6876885317
418059 gb zn56d05s1 Stratagene muscle 937209 AA211586 62 1186 5703
437330 Homo sapiens mRNA, cDNA DKFZp761J1112 (AL353944 Hs 50115 i 6 2 3253 7250
420576 KIAA1858 protein AA297634 Hs 54925 62 1463 5914
413795 ESTs AL040178 Hs 142003 62 743 5358
412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 62 569 5220
410611 KIAA1628 protein AW954134 Hs 20924 6 1 480 5148
449595 ESTs AW293799 Hs 255238 6 1 4098 7979
418140 microfibnllar-associated protein 2 BE613836 Hs 83551 61 1196 5713
421579 stem cell growth factor, lymphocyte sec NM_002975 Hs 1 05927 61 1667 15685987
414142 hemicentin (fibulm 6) AW368397 Hs 334485 61 781 5390
451598 ESTs N29102 Hs 79658 61 4241 8093
434326 reticulon 2 NM 005619 Hs 3803 60 304330447073
453859 myogenic factor 6 (herculin) NM 002469 Hs 35937 60 4451 44528267
417944 collagen, type V, alpha 2 AU077196 Hs 82985 60 1172 5693
417389 midkine (neuπte growth promoting facto BE260964 Hs 82045 60 1109 5647
452063 ESTs, Weakly similar to TWSTJHUMAN TWIS R5318E i Hs 32366 60 4281 8124
449717 cerebral cell adhesion molecule AB040935 Hs 23954 60 41104111 7989
412755 ESTs, Weakly similar to P4HA HUMAN PROL BE144306 Hs 179891 60 637 5274
421823 ESTs N40850 Hs 28625 60 1600 6011
426935 collagen, type I, alpha 1 NMJ00088 Hs 1 72928 60 228822896498
424734 ESTs A1217685 Hs 96844 60 1992 6293
408349 homeo box C10 BE546947 Hs 44276 60 213 4949
452360 ESTs AI742082 Hs 98539 60 4321 8158
449238 muscle specific RING-fiπger protein 3 AA428229 Hs 331561 59 4075 7957
431457 integrin, alpha 11 NM_012211 Hs 256297 59 278727886870
420067 Homo sapiens mRNA, cDNA DKFZp5640222 (f T52431 Hs 94795 59 1414 5876
412472 ESTs AW975398 Hs 293836 59 593 5240
408486 sodium channel, voltage gated, type IV, L04236 Hs 46038 59 2282294960
421155 lysyl oxidase H87879 Hs 102267 59 1512 5950
429823 ESTs AA459443 Hs 181400 59 2613 6744
439751 Homo sapiens mRNA full length insert cD AA196090 Hs 50794 59 3428 7411
415655 ESTs W05433 Hs 352293 59 932 5506
452223 hypothetical protein MGC2827 AA425467 Hs 8035 58 4302 8142
430223 nephroblastoma overexpressed gene NM-002514 Hs 235935 58 2661 2662 6779
415656 ESTs W84346 Hs 84673 58 933 5507
417045 Homo sapiens ORF1 F01180 Hs 332030 58 1066 5610
422667 ESTs H25642 Hs 132821 58 1723 6102
415702 gb HSPD18414 HM3 Homo sapiens cDNA clon F28877 Hs 73680 58 942 5515
435101 ESTs AI743156 Hs 131064 58 3106 7124
410108 OSBP-related protein 6 AA081659 Hs 318775 58 423 5108
429359 mafπx metalloproteinase 14 (membrane i W00482 Hs 2399 58 2551 6702
403081 NM-.003319* Homo sapiens titin (TTN), mR 57 4704
442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 57 3551 7523
417027 triadin AA192306 Hs 23926 57 1062 5607
442295 Homo sapiens cDNA FLJ11469 fis, clone H AI827248 Hs 224398 57 3555 7527
445417 a disintegnn like and metalloprotease AK001058 Hs 12680 57 3766 7705
410295 nidogen (eπaclm) AA741357 Hs 356624 57 450 5127
448595 KIAA0644 gene product AB014544 Hs 21572 57 401540167910
450506 fibroblast activation protein, alpha NM_004460 Hs 4 18 57 41704171 8037
414482 endothelm receptor type A S57498 Hs 76252 57 8248255426
411021 Win F00055 Hs 172004 57 508 5169
453514 ESTs AA036675 Hs 50918 57 4424 8245
452023 KIAA1173 protein AB032999 Hs 27566 57 4271 42728118
409944 four and a half LIM domains 3 BE297925 Hs 57687 56 399 5090
439979 hypothetical protein FLJ10430 AW600291 Hs 6823 56 3442 7424
414359 cadheπn 11, type 2, OB cadhenn (osteo M62194 Hs 75929 56 808 5413
437446 ESTs, Moderately similar lo CA1C RAT CO AA788946 Hs 101302 56 3264 7259
407080 myosin, heavy polypeptide 8, skeletal m Z38133 Hs 113973 56 1051064858
429415 procollagen C-endopeptidase enhancer NM 002593 Hs 202097 55 2557 2558 6706
411396 ESTs C04646 Hs 85428 55 533 5191
401566 NM 005159 Homo sapiens actin, alpha, ca 55 4654
453983 ESTs H94997 Hs 16450 55 4476 8286
420190 hypothetical protein EST00098 AI816209 Hs 95867 55 1428 5888
447253 ESTs AW250196 Hs 103512 55 3907 7822
457458 ESTs R14439 Hs 209194 55 4553 8352
406519 C10001858 gι|6679124|ref|NP 032759 1| n 55 4808
443184 ESTs AI638728 Hs 135159 55 3607 7574
425863 Human unidentified mRNA, partial sequen U43604 Hs 159901 54 2152 6404
446904 DKFZP434H204 protein AL110226 Hs 16441 54 387538767795
448520 doublecortm and CaM kinase like 1 AB002367 Hs 21355 54 40104011 7907
449700 paraneoplaslic antigen L02867 Hs 78358 54 410841097988
452613 ESTs AA461599 Hs 23459 54 4337 8171
451917 Homo sapiens unknown mRNA AW391351 Hs 50820 54 4261 8108
439039 ESTs AI656707 Hs 48713 54 3373 7356 446142 ESTs AI754693 Hs 145968 54 3820 7748
422087 matrix metalloproteinase 2 (gelatinase X58968 Hs 111301 54 1641 6040
414002 FBJ murine osteosarcoma viral oncogene NM_006732 Hs 75678 54 7637645375
430713 eukaryotic translation elongation facto AA351647 Hs 2642 54 2726 6824
421251 enigma (LIM domain protein) Z28913 Hs 102948 54 1521 5957
406705 myosin, heavy polypeptide 8, skeletal m Z38133 Hs 113973 54 105 1064827
411000 ESTs, Weakly similar to S38383 SEB4B pr N40449 Hs 201619 54 505 5167
404977 Insulin like growth factor 2 (somatomed 53 4766
427863 MLL septm-like fusion AF189712 Hs 181002 53 237823796567
413031 phosphofructokinase, muscle BE515051 Hs 75160 53 671 5304
416982 creatine kinase, mitochondnal 2 (sarco J05401 Hs 80691 53 1055 10565602
453817 ESTs AW755253 Hs 379636 53 4442 8260
424330 Homo sapiens cDNA FLJ13596 fis, clone P AW073953 Hs 34054 53 1936 6253
407826 calpain 3, (p94) AA128423 Hs 40300 53 167 4911
414285 ESTs AA312914 Hs 71719 53 798 5405
426485 platelet-derived growth factor receptor NMJ06207 Hs 1 70040 53 223822396465
445875 Homo sapiens clone 24453 mRNA sequence AF070524 Hs 13410 53 3801 7731
448106 ESTs AI800470 Hs 171941 52 3977 7879
425292 37 kDa leucine rich repeat (LRR) protei NM 005824 Hs 1 55545 52 208320846359
414175 hypothetical protein DKFZp761D112 AI308876 Hs 103849 52 786 5394
417405 ESTs W28657 Hs 5307 52 1112 5649
409172 ESTs Z99399 Hs 122593 52 318 5031
422627 transforming growth factor, beta-induce BE336857 Hs 118787 52 1715 6097
414555 phospholipase A2, group IIA (platelets, N98569 Hs 76422 52 830 5431
426457 chimenn (chimaenn) 1 AW894667 Hs 380138 52 2229 6459
400419 Target AF084545 52 22234626
405681 G3000593* gι[10120319|emb|CAC081851| ( 52 4793
428981 ESTs, Weakly similar to ALU2_HUMAN ALU BE313077 Hs 93135 52 2497 6660
453271 ESTs AA903424 Hs 6786 52 4409 8232
439920 neurotπmin H05430 Hs 288433 52 3439 7421
440652 ESTs AI216751 Hs 143977 51 3478 7456
435793 KIAA1313 protein AB037734 Hs 4993 5 1 315231537162
416084 deoxythy idylate kinase (thymidylate ki L16991 Hs 79006 51 9729735540
437395 hypothetical protein DKFZp762M136 AL365408 Hs 351747 51 3258 3259 7254
412564 cardiac ankynn repeat protein X83703 Hs 355934 51 6066075251
415705 coilm U06632 Hs 966 51 943 9445516
414683 hypothetical protein MGC12702 S78296 Hs 76888 51 8468475444
411573 KIAA1077 protein AB029000 Hs 70823 51 5425435199
447321 Homo sapiens cDNA FLJ14028 fis, clone H AW271217 Hs 281434 5 1 3915 7827
452683 progesterone membrane binding protein AI089575 Hs 374574 51 4341 8175
427876 ESTs AI494291 Hs 369171 51 2381 6569
437681 Homo sapiens, Similar to TEA domain fam AI207958 Hs 166556 51 3280 7273
417308 KIAA0101 gene product H60720 Hs 81892 51 1094 5634
419235 neurotnmm AW470411 Hs 288433 51 1320 5804
443164 ESTs, Weakly similar to ALU1JHUMAN ALU AI038503 Hs 55780 5 1 3606 7573
427647 Homo sapiens cDNA FLJ20653 fis, clone K W19744 Hs 180059 50 2354 6548
409826 hypothetical protein FLJ23412 AW501112 Hs 353013 50 388 5082
418532 neurotrophic tyrosine kinase, receptor, F00797 Hs 374321 50 1252 5753
443883 serine (orcysteine) proteinase inhibit AA114212 Hs 9930 50 3653 7614
439627 hypothetical protein FLJ21841 BE621702 Hs 29076 50 3411 7394
425256 coilapsin response mediator protein 1 BE297611 Hs 155392 50 2074 6352
428560 ESTs, Weakly similar to B47411 ADPπbos AI243209 Hs 98669 50 2453 6627
430147 hairy/enhancer-of-split related with YR R60704 Hs 234434 50 2652 6773
427418 LAT1-3TM protein AA402587 Hs 356667 50 2327 6527
426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 50 2219 6453
410036 calsequestnn 2 (cardiac muscle) R57171 Hs 57975 50 412 5100
417068 hypothetical protein MGC3169 AA451910 Hs 85852 50 1069 5613
416729 Ras-related associated with diabetes U46165 Hs 1027 50 1026 10275581
433839 ESTs, Weakly similar to ALU1_HUMAN ALU F35430 Hs 146070 50 3008 7043
453874 collagen, type XIV, alpha 1 (undulm) AW591783 Hs 36131 50 4456 8270
425247 matπx metalloproteinase 11 (stromelysi NM_005940 Hs 1 55324 50 207220736351
413278 interferon-stimulated protein, 15 kDa BE563085 Hs 833 49 695 5322
416208 ESTs, Weakly similar to MUC2 HUMAN MUCI AW291168 Hs 41295 49 981 5548
424893 Homo sapiens cDNA FLJ 13303 fis, clone O AW295112 Hs 153648 49 2020 6313
457211 ESTs, Weakly similar to S51797 vasodila AW085961 Hs 130093 49 4549 8344
453341 adenylyl cyclase-associated protein 2 AI758912 Hs 296341 49 4414 8237
433012 ATX1 (antioxidant protein 1, yeast) hom NM 004045 Hs 279910 49 2925 29266978
429524 KIAA1211 protein AB033037 Hs 205293 49 25772578 6720
422599 non metastatic cells 1, protein (NM23A) BE387202 Hs 118638 49 1710 6092
407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 49 166 4910
434398 serum-inducible kinase (SNK) AA121098 Hs 3838 49 3052 7079
458247 ESTs AW580932 Hs 164170 49 4572 8368
417089 Homo sapiens cDNA FLJ21909 fis, clone H52280 Hs 18612 49 1077 5619
447436 Homo sapiens cDNA FLJ21449 fis, clone AI932971 Hs 18593 49 3928 7837
454024 hypothetical protein FLJ23403 AA993527 Hs 293907 49 4481 8290
433447 neuronal pentraxm II U29195 Hs 3281 48 29802981 7021
434747 ESTs AA837085 Hs 372254 48 3073 7097
429707 matrix metalloproteinase 23B W76631 Hs 211819 48 2606 6738
438964 ESTs AA148982 Hs 29068 48 3371 7354
435977 brain specific membrane-anchored protei AL138079 Hs 5012 48 3166 7174
435367 for muscle specific ring finger 2 AI917684 Hs 85524 48 3119 7135
439687 ESTs W94546 Hs 124747 48 3417 7400
426919 ELAV (embryonic lethal, abnormal vision AL041228 Hs 166109 48 2284 6495
450676 ESTs AI147155 Hs 279727 48 4180 8045
419081 ESTs AI798863 Hs 87191 48 1299 5788
429139 ESTs F09092 Hs 66087 48 2517 6675 416433 ESTs AI658904 Hs 84673 48 1004 5566
419250 U5 snRNP-specific protein, 116 kD AW770185 Hs 356066 48 1322 5806
433122 ESTs AB019391 Hs 58049 48 2941 6991
410687 lysyl oxidase-like 1 U24389 Hs 65436 48 4854865153
432304 ESTs AA932186 Hs 69297 48 2863 6927
413132 protein kinase (cAMP-dependent, catalyt NM_006823 Hs 75209 48 6836845314
417376 LIM protein (similar to rat protein kin AA253314 Hs 154103 47 1107 5645
438085 ESTs R52518 Hs 7967 47 3299 7292
428309 cellular retmoic acid binding protein M97815 Hs 183650 47 2427 2428 6608
421778 actin related protein 2/3 complex, subu AA428000 Hs 283072 47 1591 6003
445363 tubulm-specific chaperoπe d NM 005993 Hs 1 2570 47 376237637702
429930 ESTs AI580809 Hs 352364 47 2623 6751
421913 osteoglyciπ (osteoinductive factor, mim AI934365 Hs 109439 47 1611 6020
419968 interleukin 6 (interferon, beta 2) X04430 Hs 93913 47 1399 14005866
422110 secreted protein, acidic, cysteine-nch AI376736 Hs 121555 47 1648 6045
402331 C19001390 gι|399116|sp|P13688|BGP1 HUMA 47 4679
413482 ESTs AA129869 Hs 197143 47 727 5344
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 47 2099 21006369
412926 macrophage myπstoylated alanine-nch C AI879076 Hs 75061 47 655 5290
430643 MEGF10 protein AW970065 Hs 287425 47 2717 6817
445669 ESTs AI570830 Hs 174870 47 3789 7721
423648 hypothetical protein FLJ20449 AK000456 Hs 130546 47 1833 18346184
414961 myosin binding protein H U27266 Hs 927 47 896 8975479
408491 ESTs AI088063 Hs 7882 47 230 4961
421016 transcription factor 3 (E2A immunoglobu AA504583 Hs 101047 46 1497 5937
411411 ESTs Weakly similar to KIAA1330 protei AA345241 Hs 55950 46 537 5194
451292 KIAA1295 protein AB037716 Hs 26204 46 4221 42228079
422737 collagen, type III, alpha 1 (Ehlers-Dan M26939 Hs 119571 46 1730 1731 6108
410628 ESTs, Moderately similar to similar to AI131408 Hs 68756 46 483 5151
412560 CCR4-NOT transcription complex, subunit R24601 Hs 350495 46 602 5248
441389 endocytic receptor (macrophage mannose AF134838 Hs 7835 46 351435157488
440650 Human DNA sequence from PAC 75N13 on ch R44692 Hs 326801 46 3477 7455
453935 ESTs AI633770 Hs 42572 46 4470 8281
407228 hemoglobin, beta M25079 Hs 155376 46 124 1254876
441611 ESTs AW590829 Hs 133463 46 3528 7500
450358 coronin, actin binding protein, 2B AB010098 Hs 24907 46 415741588027
456816 hypothetical protein FLJ10647 AK001509 Hs 144391 46 4531 45328334
424687 matrix metalloproteinase 9 (gelatiπase J05070 Hs 151738 46 1986 19876289
422648 Melanoma associated gene D86983 Hs 118893 46 1720 1721 6100
453041 Homo sapiens cDNA FLJ11918 fis, clone H AI680737 Hs 289068 46 4384 8211
421848 collagen type VI, alpha 1 X15880 Hs 108885 46 1602 16036013
451195 mesenchyme homeo box 1 U10492 Hs 438 46 421842198077
429505 a disintegnn and metalloproteinase dom AW820035 Hs 278679 46 2576 6719
424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs 93135 45 1907 6235
424800 MyoD family inhibitor AL035588 Hs 153203 45 200220036300
427809 lipoprotein lipase M26380 Hs 180878 45 2373 6562
446681 kendπn AJ003624 Hs 15896 45 3869 7789
443402 elastin (supravalvular aortic stenosis, U77846 Hs 9295 45 361936207585
428862 SRY (sex determining region Y)-box 9 (c NM 000346 Hs 2316 45 248324846650
420486 caveolm 3 AF036365 Hs 98303 45 1456 14575909
409553 semaphonn Y AF055020 Hs 54937 45 3593605060
424870 ESTs T15545 Hs 244624 45 2014 6308
452036 sema domain, seven thrombospondm repea NM_003966 Hs 27621 45 427342748119
422562 AE-binding protein 1 AI962060 Hs 118397 45 1700 6085
422424 prostate differentiation factor AI186431 Hs 296638 45 1681 6070
438704 ESTs AI435060 Hs 6705 45 3349 7334
424634 cartilage intermediate layer protein, n NMJ03613 Hs 1 51407 45 1981 19826285
437117 ESTs AL049256 Hs 122593 45 3235 7234
457411 iroquois-class homeobox protein IRX2 AW972881 Hs 276507 45 4552 8349
423013 secreted modular calcium binding protei AW875443 Hs 22209 45 1769 6135
441689 ESTs AI123705 Hs 289068 45 3533 7505
416391 mesoderm specific transcript (mouse) ho AI878927 Hs 79284 45 999 5562
419648 thyroid hormone responsive SPOT14 (rat) T73661 Hs 91877 45 1366 5839
447205 ESTs, Moderately similar to T17372 plas BE617015 Hs 11006 45 3900 7816
451820 ESTs AW058357 Hs 199248 45 4260 8107
439755 B7 homolog 3 AW748482 Hs 77873 45 3430 7413
418994 seleclin E (endothelial adhesion molecu AA296520 Hs 89546 45 1290 5781
432503 ESTs AA551196 Hs 188952 44 2878 6940
421814 thrombospondm 2 L12350 Hs 108623 44 1596 15976008
424066 ESTs, Weakly similar to I38022 hypothet Z99348 Hs 112461 44 1891 6223
412563 ESTs, Weakly similar to I38022 hypothet Z25372 Hs 350621 44 605 5250
446619 secreted phosphoprotein 1 (osteopontm, AU076643 Hs 313 44 3861 7782
409182 ESTs AA064970 Hs 376137 44 320 5033
453079 LIM protein (similar to rat protein kin AW160480 Hs 154103 44 4387 8214
417259 chondroitin sulfate proteoglycan 2 (ver AW903838 Hs 81800 44 1092 5632
424262 DKFZP564C103 protein BE294493 Hs 144058 44 1924 6245
413333 fibroblast growth factor 1 (acidic) M74028 Hs 75297 44 703 5327
408443 ESTs N33937 Hs 10336 44 222 4956
422809 hypothetical protein FLJ10549 AK001379 Hs 121028 44 1741 17426115
420895 gb yw23b03 r1 Morton Fetal Cochlea Homo H88685 44 1489 5932
419682 paired like homeodomam transcription f H13139 Hs 92282 44 1368 5841
433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 44 2923 29246977
447357 ESTs AI375922 Hs 132821 44 3917 7829
414467 copine II AW903820 Hs 85752 44 821 5424
413289 forkhead box L2 AA128061 Hs 289292 44 696 5323
407239 leukocyte immunoglobulm-like receptor, AA076350 Hs 67846 44 129 4879 446962 muscle specific ring finger protein 1 AI351421 Hs 279709 44 38847801 423922 muscle-specific beta 1 integrin binding AK001663 Hs 135458 44 187118726210 425262 GS3955 protein D87119 Hs 155418 44 207620776354 417421 nuclear receptor subfamily 4, group A, AL138201 Hs 82120 44 11185653 418283 cathepsin K (pycnodysostosis) S79895 Hs 83942 44 121012115724 419407 hypothetical protein FLJ21276 AW410377 Hs 41502 43 13345817 453221 ESTs AW590263 Hs 232311 43 44048228 426395 hypothetical protein FLJ23316 BE151985 Hs 355669 43 22176451 436411 gb ba63c07y1 NIHJIGCJ2 Homo sapiens C AW674352 Hs 29383643 31857190 423057 ESTs, Moderately similar to I38022 hypo AW961597 Hs 130816 43 17736139 441104 ESTs AI382357 Hs 143903 43 34997474 410762 HSKM B protein AF226053 Hs 66170 43 4924935157 414715 amylo-1,6 glucosidase, 4-alpha glucanot AA587891 Hs 904 43 8555450 433209 KIAA1474 protein AB040907 Hs 278436 43 295329546999 418036 latent transforming growth factor beta Z37976 Hs 83337 43 118011815699 440087 hypothetical protein FLJ22678 W28969 Hs 7718 43 34527433 417160 proteolipid protein 1 (Pelizaeus-Merzba N76497 Hs 355807 43 10865626 420456 SH3 domain binding protein 1 Z83844 Hs 97858 43 3281 5906 428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs 337534 43 23936579 451154 ESTs AA015879 Hs 33536 43 42158074 410929 ESTs H47233 Hs 30643 43 5045166 423563 protein kinase (cAMP dependent, catalyt R34734 Hs 75209 43 18176171 411929 ESTs AA098880 Hs 69297 43 5615213 427826 myomegalin AL043194 Hs 265848 43 23756564 430702 H factor 1 (complement) U56979 Hs 250651 43 272427256823 415885 KIAA0161 gene product D79983 Hs 78894 43 9539545524 437696 hypothetical protein dJ37E165 Z83844 Hs 5790 43 3281 7274 453452 ESTs AI080235 Hs 174497 43 44208242 421307 Homo sapiens mRNA cDNA DKFZp434B0425 ( BE539976 Hs 10330543 15285963 433043 lymphoid nuclear protein (LAF-4) mRNA W57554 Hs 125019 43 29306982 426054 ELAV (embryonic lethal, abnormal vision U12431 Hs 166109 43 216421656413 449342 hypothetical protein DKFZp434D1428 AA814517 Hs 321775 43 40827964 403088 NMJ03319* Homo sapiens titin (TTN), mR 43 4707 436315 hypothetical protein MGC4837 BE390513 Hs 27935 43 31827187 407711 KIAA1808 protein AI085846 Hs 25522 42 1514896 422414 ESTs AW875237 Hs 132160 42 16806069 432943 HSPC018 protein AW575160 Hs 283677 42 29176971 443105 chondroitin sulfate proteoglycan 4 (mel X96753 Hs 9004 42 360036017568 450534 KIAA0470 gene product AI570189 Hs 25132 42 41758040 431632 Homo sapiens cDNA FLJ10130 fis, clone H AK000992 Hs 333144 42 28046882 452195 ESTs AA994712 Hs 116878 42 42968138 448386 KIAA1329 protein AB037750 Hs 21061 42 399739987896 409716 Homo sapiens mRNA cDNA DKFZp586J1717 ( AL117454 Hs 56027 42 3835077 417796 ESTs AA206141 Hs 367818 42 11595682 410055 gene for seπne/threonine protein kiπas AJ250839 Hs 58241 42 4144155102 420582 Homo sapiens chromosome 19, cosmid R283 BE047878 Hs 99093 42 14645915 417675 similar to murine leucine-nch repeat p AI808607 Hs 3781 42 11445670 424806 MSTP031 protein AA382523 Hs 105689 42 20046301 438072 ESTs AA992149 Hs 121899 42 32977290 407330 gb nn51b05 s1 NCI CGAP Kιd6 Homo sapien AA582607 Hs 15628942 1364884 416857 FGENESH predicted TM containing protein AA188775 Hs 292453 42 10425592 439737 Homo sapiens mRNA full length insert cD AI751438 Hs 41271 42 34277410 423914 Human DNA sequence from clone RP3-466N1 BE379485 Hs 135259 42 18686208 425494 ESTs, Weakly similar to similar to anky N55540 Hs 78026 42 21076374 423171 hypothetical protein DKFZp761G1913 AW138498 Hs 245880 42 17786143 451811 hypothetical protein MGC1136 AA663485 Hs 8719 42 42598106 408449 dynamin l NMJ04408 Hs 1 66161 42 2242254958 409882 heat shock 27kD protein family, member AJ243191 Hs 56874 42 3953965087 443163 ESTs AI082610 Hs 132079 42 36057572 456508 ESTs, Weakly similar to AF208855 1 BM 0 AA502764 Hs 123469 42 4521 8325 454090 gb MRO-CT0064-100899-002-h09 CT0064 Hom AW062462 42 44908298 432211 hypothetical protein FLJ10986 BE274530 Hs 273333 42 28526917 431830 small inducible cytokine subfamily A (C Y16645 Hs 271387 42 282728286900 445677 ras homolog gene family, member E H96577 Hs 6838 42 37917723 417114 ESTs AA193472 Hs 20007 42 10805621 400653 NM_001104* Homo sapiens actinin, alpha 42 4637 433323 ESTs AA805132 Hs 159142 42 29707011 420139 lipase, hormone sensitive NMJ05357 Hs 95351 42 141914205881 447946 ESTs AI566164 Hs 277445 42 39687870 445263 KIAA1560 protein H57646 Hs 42586 42 37557697 407896 Zic family member 1 (odd-paired Drosoph D76435 Hs 41154 42 1761774919 428317 ESTs AW022609 Hs 50745 42 2431 6610 415668 Homo sapiens lysyl oxidase-like 4 (LOXL AW957684 Hs 306814 42 9365510 414774 plasminogen activator, urokinase X02419 Hs 77274 42 8698705461 431103 pleiotrophin (hepaπn binding growth fa M57399 Hs 44 42 274827496840 425712 ESTs, Moderately similar to ALULHUMAN AA412548 Hs 21423 42 21306389 408202 DKFZP586L151 protein AA227710 Hs 43658 41 2024942 424119 ESTs AI141999 Hs 113314 41 18996229 426369 Kreisler (mouse) maf-related leucine zi AF134157 Hs 169487 41 221322146448 453876 ESTs, Weakly similar to I38022 hypothet AW021748 Hs 110406 41 44578271 435406 calcium/calmodulin dependent protein ki F26698 Hs 4884 41 31247140 429951 zinc finger protein 106 AL040521 Hs 15220 41 26246752 408920 fibroneclin leucine rich transmembrane AL120071 Hs 48998 41 2764999 444412 Homo sapiens clone HH409 unknown mRNA AI147652 Hs 216381 41 37007655 450336 Homo sapiens cDNA FLJ23296 fis, clone AA046814 Hs 288928 41 41558025 414117 proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs 355807 41 7775386 429317 Homo sapiens cDNA FLJ21243 fis, clone AA831552 Hs 268016 41 2544 6696
416783 monocyte to macrophage differentiation- AA206186 Hs 79889 41 1031 5584
450842 ESTs AA011358 Hs 103316 41 4200 8061
451669 Homo sapiens clone IMAGE 3603836, mRNA AA349726 Hs 294151 41 4243 8095
416728 casein kinase 1, epsilon AB024597 Hs 79658 41 1024 10255580
452991 ESTs AI393659 Hs 375560 41 4376 8204
413004 interleukin enhancer binding factor 2, T35901 Hs 75117 41 667 5300
448866 myogenic factor 3 BE297743 Hs 284203 41 4044 7932
447628 ESTs AI914617 Hs 161353 41 3943 7850
452242 gycosyltransferase R50956 Hs 159993 41 4305 8145
426996 Homo sapiens cDNA FLJ21897 fis, clone AW968934 Hs 173108 41 2295 6503
407965 heat shock 27kD protein 3 W21483 Hs 41707 41 183 4925
428303 regulator of G protein signalling 16 AW974476 Hs 183601 41 2425 6606
439450 ESTs R51613 Hs 125304 41 3397 7380
435937 ESTs AA830893 Hs 119769 41 3164 7172
433972 cisplatin resistance-associated overexp AI878910 Hs 278670 41 3021 7054
428418 ESTs AI368826 Hs 8768 41 2441 6619
423550 ESTs F37675 Hs 152129 41 1815 6169
406627 ESTs T64904 Hs 163780 41 30 4812
436555 ESTs, Weakly similar to 2003319A ankyπ AI972007 Hs 304646 41 3200 7202
408696 NS1-assocιated protein 1 AW958157 Hs 355960 41 249 4979
426433 thrombospondm 3 L38969 Hs 169875 41 222622276457
408753 SH3 domain binding glutamic acid-nch p AI337192 Hs 47438 41 254 4983
409038 small inducible cytokine subfamily A (C T97490 Hs 50002 41 298 5016
416140 roundabout (axon guidance receptor, Dro AI918035 Hs 301198 40 978 5545
422961 B cell CLUIymphoma 9 Y13620 Hs 122607 40 1763 17646131
446508 hypothetical protein FLJ13441 H11701 Hs 232146 40 3844 7768
430558 KIAA1067 protein AB028990 Hs 325530 40 27102711 6813
411127 hypothetical protein AA668995 Hs 323463 40 516 5176
446019 histone deacetylase 3 AI362520 Hs 302718 40 3810 7739
415580 ESTs Weakly similar to ALU1JHUMAN ALU F12306 Hs 369191 40 931 5505
417994 cytotoxic T lymphocyte associated prate A1791416 Hs 247824 40 1173 5694
421937 hematological and neurological expresse : AI878857 Hs 109706 40 1617 6024
446510 retinoic acid induced 14 H58306 Hs 15165 40 3847 7770
426817 Homo sapiens mRNA, cDNA DKFZp564C0671 ( AL122088 Hs 17262740 2276 6488
421483 hypothetical protein MGC11333 NM 003388 Hs 1 04717 40 1545 15465973
412473 ESTs F23393 Hs 153060 40 594 5241
424223 putative DNA/chromatin binding motif AJ243706 Hs 143323 40 1915 19166240
449030 Homo sapiens mRNA for FLJ00016 protein, AI365582 Hs 57100 40 4059 7943
426344 transcriptional activator of the c-fos H41821 Hs 322469 40 2209 6445
432787 HSPC054 protein NMJ14152 Hs 278946 40 2905 2906 6962
426304 Homo sapiens cDNA FLJ11477 fis, clone H AA374532 Hs 124673 40 2198 6438
419290 spinal cord derived growth factor-B AI128114 Hs 112885 40 1327 5810
406850 collagen, type I, alpha 1 AI624300 Hs 172928 40 70 4837
401284 Target Exon 40 4648
448121 hypothetical protein DKFZp564F013 AL045714 Hs 128653 40 3979 7881
448646 transcription factor 12 (HTF4, helix-lo AU077149 Hs 21704 40 4022 7914
459578 EST 40 8391
440594 ESTs AW445167 Hs 126036 40 3475 7453
419452 PTK7 protein tyrosine kinase 7 U33635 Hs 90572 40 1340 1341 5821
424511 ESTs, Moderately similarto ALU7 HUMAN BE300512 Hs 193557 40 1967 6276
443072 gb wp78d02x1 NCI_CGAP_Brn25 Homo sapie AI937532 Hs 353026 40 3599 7567
429713 thioredoxin, mitochondπal N41898 Hs 211929 40 2608 6740
446452 KIAA0740 gene product AB018283 Hs 15099 39 383938407765
451678 DKFZP564D0764 protein AA374181 Hs 26799 39 4244 8096
419940 ESTs AW611903 Hs 144585 39 1397 5864
415024 ESTs AI983981 Hs 296141 39 902 5483
445470 ESTs AI239871 Hs 154758 39 3772 7710
418399 hypothetical protein FLJ12442 AF131781 Hs 84753 39 1232 12335738
413929 collagen, type IV, alpha 2 BE501689 Hs 75617 39 754 5368
430030 lectin, galactoside binding, soluble, 1 BE300094 Hs 227751 39 2641 6764
452701 glutamine fructose-6-phosphate transam i NM_005110 Hs 30332 39 43454346 8178
426363 transforming growth factor, beta 3 M58524 Hs 2025 39 22102211 6446
445900 Homo sapiens clone 24787 mRNA sequence AF070526 Hs 125036 39 3803 7733
435520 HNOEL-iso protein AA297990 Hs 9315 39 3130 7146
411962 gb zk85d12 r1 Soares_pregnant_uterus- Nb AA099050 39 563 5215
432098 cytochrome P450 retinoid metabolizing p AF252297 Hs 91546 39 283928406908
418647 gb nc26a07 s1 NCI CGAP Pr1 Homo sapiens AA226198 38 1263 5761
452277 KIAA1223 protein AL049013 Hs 28783 38 4308 8148
408562 roundabout (axon guidance receptor, Dro AI436323 Hs 31141 38 240 4971
452239 protein tyrosine phosphatase, receptor AW379378 Hs 356289 38 4303 8143
439424 hypothetical protein FLJ22833 AI478667 Hs 118183 38 3396 7379
433430 ESTs AI863735 Hs 369982 38 2977 7018
439673 Homo sapiens cDNA FLJ22290 fis, clone T53169 Hs 9587 38 3416 7399
451691 ESTs AI809278 Hs 208152 38 4248 8099
417024 ESTs A1467951 Hs 133326 38 1061 5606
443617 papillary renal cell carcinoma (translo AA496425 Hs 9629 38 3629 7592
435553 KIAA0176 protein D79998 Hs 4935 38 313431357149
434868 collagen, type VI, alpha 2 R50032 Hs 159263 37 3085 7106
441965 ESTs AA972712 Hs 269737 37 3544 7516
422565 singed (Drosophila) like (sea urchin fa BE259035 Hs 118400 37 1701 6086
429290 neurofilament, heavy polypeptide (200kD AF203032 Hs 198760 37 25382539 6692
416322 pyrrol e 5 carboxylate reductase 1 BE019494 Hs 79217 37 989 5554
432842 hypothetical protein MGC4485 AW674093 Hs 334822 37 2911 6966
430818 gb qo89h04 x1 NCI_CGAP_Kιd5 Homo sapien A1311928 Hs 348156 37 2728 6826
442578 hypothetical protein FLJ10781 AK001643 Hs 8395 37 357235737543 422084 hypothetical protein AK001266 Hs 111279 37 163716386038 426316 meningioma (disrupted in balanced trans NM_002430 Hs 268515 37 220322046441 418745 sprouty (Drosophila) homolog 1 (antagoπ AW882645 Hs 88044 37 12735768 412978 homeo box C6 AI431708 Hs 820 37 6655298 425741 Homo sapiens clone 24628 mRNA sequence AF052152 Hs 129997 37 21336391 414358 ESTs AA476456 Hs 98969 36 8075412 432179 EphB3 X75208 Hs 2913 36 284928506915 442831 ESTs AI798959 Hs 131686 36 35867554 453327 tryptophanyl-tRNA synthetase AW500180 Hs 356109 36 44128235 407454 gb Homo sapiens mRNA for axonemal dynei AJ132089 36 1401414887 427375 metallocarboxypeptidase CPX-1 AL035460 Hs 177536 36 232023216522 421920 gamma-aminobutyπc acid (GABA) receptor BE551245 Hs 1438 36 16146022 448111 interferan-induced protein with tetratr AA053486 Hs 20315 36 39787880 410422 Homo sapiens, clone MGC 15203, mRNA, co AL042014 Hs 63348 36 4625136 418741 ESTs, Weakly similar to S41044 chromoso H83265 Hs 8881 36 12725767 416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 35 100110025564 431176 ESTs AI026984 Hs 293662 35 27556844 448412 ESTs, Moderately similarto ALU8_HUMAN AI219083 Hs 42532 35 40027899 417426 laminin, beta 1 NMJ02291 Hs 82124 35 111911205654 447471 sprouty (Drosophila) homolog 2 AF039843 Hs 18676 35 393039317839 414612 protein inhibitor of activated STAT3 BE274552 Hs 76578 35 8385438 430598 hypothetical protein FLJ10902 AK001764 Hs 247112 35 271227136814 407325 ESTs, Weakly similar to alternatively s AA291180 Hs 328476 35 1354883 443228 KIAA1710 protein W24781 Hs 293798 34 36107577 406972 gb Human H19 RNA gene, complete eds M32053 34 894848 439668 fπzzled (Drosophila) homolog 8 AI091277 Hs 302634 34 34147397 458300 πbosomal protein L31 AW612538 Hs 304491 34 45738370 448309 N deacetylase/N-sulfotransferase (hepar AI282120 Hs 20894 34 39937892 410023 slit (Drosophila) homolog 3 AB017169 Hs 57929 34 4104115099 453905 LIM domain kinase 1 NM 002314 Hs 36566 34 446244638276 435189 ESTs AW581418 Hs 196244 34 31137131 447809 ESTs, Highly similar to JC72663 ,5'-cy AW207605 Hs 164230 34 39647866 429709 dickkopf (Xenopus laevis) homolog 2 BE047680 Hs 211869 33 26076739 424651 ESTs AI493206 Hs 120785 33 19846287 422048 spondin 2, extracellular matrix protein NM..012445 Hs 288126 33 163116326034 441499 ESTs AW298235 Hs 101689 33 35227495 437036 ESTs AI571514 Hs 133022 33 32327231 409430 splicing factor, arginine/seππe rich 5 R21945 Hs 346735 33 3485052 407137 gb ye53h05 si Soares fetal liver spleen T97307 32 1144866 409433 ESTs AA074382 Hs 135255 32 3495053 429640 angiopoietm 1 U83508 Hs 2463 32 259625976732 442828 FK506 binding protein 9 (63 kD) BE263255 Hs 302749 32 35857553 450161 ESTs H78516 Hs 201362 32 41378012 439456 hypothetical protein FLJ20980 AI752409 Hs 109314 32 34007383 440614 hypothetical protein FLJ12879 AA781530 Hs 127236 32 34767454 417043 collagen, type VI, alpha 3 NM 004369 Hs 80988 31 106410655609 426027 platelet-derived growth factor beta pol NMJ02608 Hs 1 976 31 216121626411 409197 chromosome 11 open reading frame 24 \N54706 Hs 303025 31 3225035 442487 hypothetical protein, estradiol-mduced AF191019 Hs 8361 31 356435657536 456856 Homo sapiens, Similar to DiGeorge syndr AK001528 Hs 347285 30 45338335
TABLE 3B
Pkey Unique Eos probeset identifier number CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
418059 11644381 AA211586 F35799 F29720 AW937408 AW937387 AA211641
426413 3724681 AW954494 AA377823 BG219617 BG195685 BG616269 AI022688
420895 2636041 AA557228 AI275977 H88644 AA281495 H88685
454090 5798941 AW062465 AW062462 BF333918 AW176554 AW062482 AW062481 AW062468 AW062467
459578 9964331 BE937231 FJI712437 A 612538 BI712664 BI712740 BI712501
411962 23077101 AA099050AA099526T47733
418647 2436801 AA226513 AA383773 AA226198
TABLE 3C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers Dunham I et al " refers to the publication entitled "The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495 Strand Indicates DNA strand from which exons were predicted
N position Indicates nucleotide positions of predicted exons Pkey Ref Strand NLposition
405001 6015406 Minus 104646-104819
400499 9796071 Minus 148495-148806
400651 8117978 Minus 81488 81646
402621 9930950 Plus 130806-131036 403081 8954241 Plus 155749-156048,156142-156459
401566 8469090 Minus 96277-96420,96979-97160
406519 3962489 Plus 34617-34928
404977 3738341 Minus 43081-43229
405681 4544348 Minus 79420-79605 402331 8050898 Minus 53610-53888
403088 8954241 Plus 169894-170193,170504-170806 400653 8117978 Plus 109077-109307 401284 9800819 Minus 101307-101421
TABLE4A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of liposarcoma AIs divided by the 50th percentile of normal tissue AIs, where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQID#
413778 myosin, light polypeptide 2, regulatory AA090235 Hs 75535 373 7405356
407245 titin X90568 Hs 172004 285 1321334881
426752 X69490 Hs 172004 224 226622676482
425545 Homo sapiens, clone MGC 12401, mRNA, co N98529 Hs 158295 21 0 21146379
412519 troponin T1, skeletal, slow AA196241 Hs 73980 199 5985244
400440 nebulm X83957 Hs 83870 190 24254627
426300 delta like homolog (Drosophila) U15979 Hs 169228 18 8 219621976437
407013 gb Human nebulm mRNA, partial eds U35637 Hs 83870 183 94954851
453857 Ras induced senescence 1 (RIS1) AL080235 Hs 35861 18 1 444944508266
416931 adipose most abundant gene transcript 1 D45371 Hs 80485 179 104710486597
417070 Win Z19077 Hs 172004 163 10705614
406704 myosin, heavy polypeptide 7, cardiac mu M21665 Hs 929 146 55564826
417435 carbonic anhydrase III, muscle specific NM_005181 HS 8 2129 143 112111225655
420139 lipase, hormone-sensitive NMJ05357 Hs 9 5351 141 141914205881
421296 peπlipin NM_002666 Hs 1 03253 140 152515265961
405001 interleukin enhancer binding factor 1 132 4767
428087 troponin C2, fast AA100573 Hs 182421 130 23966582
413385 indoleamine-pyrrole 2,3 dioxygenase M34455 Hs 840 129 7107115331
422060 ESTs, Moderately similar to ALU5JHUMAN R20893 Hs 325823 127 16336035
422640 troponin C, slow M37984 Hs 118845 125 171817196099
406964 FGENES predicted novel secreted protein M21305 124 87884847
419648 thyroid hormone responsive SPOT14 (rat) T73661 Hs 91877 122 13665839
427809 lipoprotein lipase M26380 Hs 180878 12 2 23736562
411393 B-factor, properdin (COMPLEMENT FACTOR AW797437 Hs 69771 12 1 5315189
458079 Homo sapiens similar to RIKEN cDNA 2810 AI796870 Hs 381220 120 45668363
418399 hypothetical protein FLJ12442 AF131781 Hs 84753 11 9 123212335738
431830 small inducible cytokine subfamily A (C Y16645 Hs 271387 11 8 282728286900
429359 matrix metalloproteinase 14 (membrane i W00482 Hs 2399 11 8 2551 6702
410621 titin AA194329 Hs 172004 11 7 4815149
425292 37 kDa leucine πch repeat (LRR) protei NMJ05824 Hs 1 55545 11 6 208320846359
453331 ESTs AI240665 Hs 352537 11 6 44138236
417389 midkiπe (neuπte growth promoting facto BE260964 Hs 82045 11 6 11095647
428182 ESTs, Weakly similar to GGC1_HUMAN G AN BE386042 Hs 293317 11 4 24036588
419222 sperm e synthase AD001528 Hs 89718 11 2 131813195803
416373 ESTs, Weakly similar to S12658 cysteine AA195845 Hs 73680 11 0 9965559
444381 hypothetical protein BC014245 BE387335 Hs 283713 109 36977652
431089 ESTs, Weakly similar to unknown protein BE041395 Hs 374629 109 27456838
410407 carbonic anhydrase IX X66839 Hs 63287 109 4604615135
411296 growth suppressor 1 BE207307 Hs 10114 107 5245183
427254 ESTs AL121523 Hs 97774 106 23126516
446619 secreted phosphoprotein 1 (osteopoπtm, AU076643 Hs 313 105 38617782
422069 titin cap (telethonin) AJ010063 Hs 343603 104 163516366037
418054 lysyl oxidase like 2 NM 002318 Hs 83354 104 118411855702
418986 ESTs AI123555 Hs 293821 104 12885779
416378 ankyπn repeat domain 2 (stretch respon AW044467 Hs 73708 103 9975560
413902 CD36 antigen (collagen type I receptor, AU076743 Hs 75613 102 7525366
411789 Adlican AF245505 Hs 72157 102 5535545207
414152 thrombospondm 4 NMJ303248 Hs 75774 101 7827835391
418478 cyclin-dependent kinase inhibitor 2A (m U38945 Hs 1174 10 1 124512465747
414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 100 7895397
429185 ESTs AW203961 Hs 104977 98 25286682
403593 Target Exon 98 4725
407102 glycerol-3-phosphate dehydrogenase 1 (s AA007629 Hs 348601 97 1094861
418391 troponin I, skeletal, slow NMJ03281 Hs 84673 96 122812295736
428769 ESTs AW207175 Hs 106771 95 24706640
407788 SlOO calcium-binding protein A2 BE514982 Hs 38991 95 1614905
449109 ESTs, Weakly similar to ALU7_HUMAN ALU AW270992 Hs 120949 94 40647948
452620 ESTs AA436504 Hs 119286 94 43388172
425367 protein tyrosine phosphatase, receptor BE271188 Hs 155975 94 20956366
418390 titin immunoglobulin domain protein (my AF133820 Hs 84665 94 122612275735
403088 NMJ03319* Homo sapiens titin (TTN), mR 93 4707
426509 pentaxin-related gene, rapidly induced M31166 Hs2050 92 224322446468
430476 tachykinin, precursor 1 (substance K, s AA447465 Hs 2563 92 27016807
419833 Homo sapiens tryptophanyl tRNA syntheta AA251131 Hs 220697 9 1 13885856
410687 lysyl oxidase like 1 U24389 Hs 65436 90 4854865153
457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 89 45618359
410361 guanylate binding protein 1, interferon BE391804 Hs 62661 89 4565132
443514 ESTs BE464288 Hs 25475 89 36247588
443071 complement component 1, q subcomponent, AL080021 Hs 8986 89 35987566
414386 haptoglobin X00442 Hs 75990 88 8108115415
450098 hypothetical protein FLJ21080 W27249 Hs 8109 87 41348009 409169 (clone PWHLC2-24) myosin light chain 2 F00991 Hs 50889 87 316 5029
413011 biglycan AW068115 Hs 821 86 669 5302
420197 ESTs, Weakly similar to A57291 cytokine AW139647 Hs 88134 85 1429 5889
418678 cancer/testis antigen (NY-ESO-1) NM 001327 Hs 87225 85 1269 12705765
450375 a disintegnn and metalloproteinase do AA009647 Hs 352537 85 4159 8028
408202 DKFZP586L151 protein AA227710 Hs 43658 84 202 4942
411021 titin F00055 Hs 172004 84 508 5169
413278 interferon stimulated protein, 15 kDa BE563085 Hs 833 84 695 5322
423739 ESTs AA398155 Hs 97600 84 1842 6190
438089 nuclear receptor subfamily 1, group I, W05391 Hs 351546 84 3301 7294
426429 myosin binding protein C, slow-type X73114 Hs 169849 84 222422256456
424408 collagen, type V, alpha 1 AI754813 Hs 146428 83 1943 6260
423778 flavin containing monooxygenase 2 Y09267 Hs 132821 83 1846 18476193
407112 ESTs, Weakly similar to ALU7_HUMAN ALU AA070801 Hs 51615 83 111 4863
417370 tryptophanyl-ΪRNA synthetase T28651 Hs 374466 82 1105 5643
451099 interleukin 13 receptor, alpha 2 R52795 Hs 26954 8 1 4212 8071
423024 ESTs, Moderately similar to ALU5_HUMAN AA593731 Hs 325823 81 1770 6136
418026 fatty acid binding protein 4, adipocyte BE379727 Hs 83213 80 1179 5698
434352 small muscle protein, X linked AF129505 Hs 86492 80 304730487075
447131 retmoic acid receptor responder (tazar NM 004585 Hs 1 7466 80 3891 38927808
452838 preferentially expressed antigen in mel U65011 Hs 30743 79 435743588188
427335 G antigen 7B AA448542 Hs 278444 79 2317 6520
431211 gap junction protein, beta 2, 26kD (con M86849 Hs 323733 78 276227636850
444006 type I transmembrane protein Fn14 BE395085 Hs 334762 78 3668 7627
400499 C10001858 gιl6679124|ref|NP 032759 1| n 78 4628
448498 ESTs AA418276 Hs 375003 78 4007 7904
447205 ESTs Moderately similar to T17372 plas BE617015 Hs 11006 77 3900 7816
412326 small inducible cytokine A3 (homologous R07566 Hs 73817 77 582 5231
427639 Homo sapiens, clone MGC 18257, mRNA, co AW444530 Hs 350860 77 2353 6547
430413 small inducible cytokine A5 (RANTES) AW842182 Hs 241392 77 2693 6801
414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 76 8768775465
409096 sarcomeπc muscle protein AA194412 Hs 50550 76 302 5019
418728 ESTs AW970937 Hs 293843 76 1271 5766
442573 branched chain ammotransferase 1, cyto H93366 Hs 7567 75 3570 7541
442069 membrane-bound transcription factor pro i AW664144 Hs 297007 75 3548 7520
437330 Homo sapiens mRNA, cDNA DKFZp761J1112 ( AL353944 Hs 50115 75 3253 7250
420137 CD3D antigen, delta polypeptide (TιT3 c AA306478 Hs 95327 75 1418 5880
428289 complement component 2 M26301 Hs 2253 75 2421 24226603
435523 membrane spanning 4 domains, subfamily T62849 Hs 11090 75 3131 7147
400288 integrin, alpha 5 (fibronectin receptor X06256 Hs 149609 74 1 24614
438746 Human melanoma associated antigen p97 ( AI885815 Hs 184727 73 3353 7337
426310 neuropeptide Y receptor Y1 NM 000909 Hs 1 69266 73 219922006439
429973 ESTs AI423317 Hs 164680 73 2628 6756
425088 hypothetical protein FLJ12015 AA663372 Hs 169395 73 2049 6334
444090 natural killer cell group 7 sequence S69115 Hs 10306 73 3675 36767634
422633 enolase 3, (beta, muscle) X56832 Hs 118804 73 1716 17176098
449722 cyclm B1 BE280074 Hs 23960 72 4112 7990
432606 granzyme K (serine protease, granzyme 3 NMJ302104 Hs 3066 72 2891 28926951
438091 nuclear receptor subfamily 1 , group I, AW373062 Hs 351546 72 3302 7295
419490 granzyme A (granzyme 1, cytotoxic T-lym NM.006144 Hs 90708 72 1343 13445823
418156 nuclear receptor subfamily 1 , group I, W17056 Hs 83623 71 1198 5715
424687 matrix metalloproteinase 9 (gelatmase J05070 Hs 151738 71 1986 19876289
417308 KIAA0101 gene product H60720 Hs 81892 70 1094 5634
423961 peπostin (OSF-2os) D13666 Hs 136348 70 1878 18796215
410021 X-prolyl aminopeptidase (aminopeptidase AL023653 Hs 57922 70 409 5098
401403 Target Exon 70 4651
406673 major histocompatibility complex, class M34996 Hs 198253 70 90 91 4821
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 70 3057 7083
421508 absent in melanoma 2 NM 004833 Hs 1 05115 70 1551 15525977
418460 CD8 antigen, alpha polypeptide (p32) M26315 Hs 85258 70 1243 12445746
430678 ESTs AI458174 Hs 192855 70 2718 6818
445937 UDP-Gal betaGlcNAc beta 1,4- galactosyl A1452943 Hs 321231 70 3807 7737
420202 putative lymphocyte G0/G1 switch gene AL036557 Hs 95910 69 1430 5890
456063 retinol-bmding protein 4, interstitial NM 006744 Hs 76461 69 4511 45128317
429500 hexabrachion (tenascin C, cytotact ) X78565 Hs 289114 68 25742575 6718
415989 ESTs AI267700 Hs 351201 68 962 5530
425234 ESTs, Weakly similar to I38022 hypothet AW152225 Hs 165909 68 2070 6349
452701 glutamιne-fructose-6-phosphate transamι NMJ05110 Hs 30332 68 43454346 8178
424825 procollagen lysine, 2 oxoglutarate 5 di AF207069 Hs 153357 68 20052006 6302
440709 ESTs AW797724 Hs 130350 68 3484 7460
424503 integπn, alpha 5 (fibronectin receptor NM 002205 Hs 1 49609 68 1965 19666275
449523 chemokme (C-C motif) receptor 5 NM 000579 Hs 54443 68 409440957976
412584 DNA segment on chromosome 12 (unique) 2 X54870 Hs 74085 67 6126135255
414812 monokiπe induced by gamma interferon X72755 Hs 77367 67 874875 5464
424086 lysyl oxidase A1351010 Hs 102267 67 1896 6227
410274 hypoxia inducible protein 2 AA381807 Hs 336402 67 444 5122
403081 NM 003319* Homo sapiens titin (TTN), R 67 4704
437220 GS1999full AL117542 Hs 334305 67 3247 7244
442553 hypothetical protein MGC4825 H87867 Hs 40065 67 3568 7539
451934 ESTs AI540842 Hs 61082 67 4262 8109
418062 thioredoxin peroxidase (antioxidant enz AW630656 Hs 83383 67 1187 5704
422627 transforming growth factor beta-induce BE336857 Hs 118787 67 1715 6097
420981 peroxisome proliferative activated rece L40904 Hs 100724 67 1495 14965936
432522 phosphatidylmositol glycan, class A (p D11466 Hs 51 66 28802881 6942
439285 hypothetical protein FLJ20093 AL133916 Hs 47860 66 3389 7372
444329 hypothetical protein FLJ12921 W73753 Hs 209637 66 3693 7648 442173 KIAA0144 gene product N76101 Hs 8127 66 35527524 407366 gb Homo sapiens cιg33 mRNA, partial seq AF026942 Hs 17518 66 1374885 427337 Fc fragment of IgG, low affinity lllb, Z46223 Hs 176663 66 231823196521 424420 prostaglandin E synthase BE614743 Hs 146688 65 19496264 419741 ubiquitin carrier protein E2-C NMJ07019 Hs 93002 65 137913805850 439092 gb oc44f08 s1 NCI_CGAP_GCB1 Homo sapien AA830149 65 33767359 422530 bone marrow stromal cell antigen 2 AW972300 Hs 118110 65 16966082 439237 ESTs, Weakly similar to A47582 B cell g AW408158 Hs 318893 65 33847367 445263 K1AA1560 protein H57646 Hs 42586 64 37557697 450447 hypothetical protein P15-2 AF212223 Hs 25010 64 416841698036 428976 ras homolog gene family, member I AL037824 Hs 194695 64 24956658 406625 stearoyl-CoAdesaturase (delta-9 desatu Y13647 Hs 119597 64 28294811 446523 sarcolipin NMJ03063 Hs 334629 64 385238537774 401566 NM-.005159 Homo sapiens actin, alpha, ca 64 4654 447770 fπzzled (Drosophila) homolog 4 ABQ32417 Hs 19545 64 396139627864 429294 Homo sapiens cDNA FLJ22463 fis, clone AA095971 Hs 198793 64 25406693 447733 MAD2 (mιtotιc arrest deficient, yeast, AF157482 Hs 19400 64 395539567860 437206 ESTs Weakly similar to 138344 Win, c AW975934 Hs 172004 64 32457242 425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 64 209921006369 406922 gb stearoyl-CoA desaturase [human, adip S70284 Hs 119597 63 79804843 406837 immunoglobulin kappa constant R70292 Hs 156110 63 694836 409142 SMC4 (structural maintenance of chromos AL136877 Hs 50758 63 3123135027 410270 tumor endothelial marker 1 precursor AF279142 Hs 195727 63 4424435121 450787 aquaporιn 7 AB006190 Hs 25475 63 419441958057 407061 gb H sapiens PTX3 gene promotor region X97748 63 1024856 429626 holocytochrome c synthase (cytochrome C U36787 Hs 211571 63 259325946730 439424 hypothetical protein FU22833 AI478667 Hs 118183 63 33967379 418113 SRY (sex determining region Y) box 4 AI272141 Hs 83484 63 11945711 418607 KIAA1402 protein AL137426 Hs 86392 62 12605759 414053 traπsgelin 2 BE391635 Hs 75725 62 7745383 426991 Homo sapiens CDNAFLJ10674 fis, clone NAK001536 Hs 214410 62 22946502 439755 B7 homolog 3 AW748482 Hs 77873 62 34307413 447519 ESTs U46258 Hs 339665 62 39367844 430699 ESTs, Weakly similar to RET2_HUMAN RETI AW969847 Hs 292718 62 27236822 426798 ESTs AA385062 Hs 130260 62 22756487 419913 ESTs AW270040 Hs 34455 62 13955862 414002 FBJ murine osteosarcoma viral oncogene NM_006732 Hs 75678 62 7637645375 424688 myosin, light polypeptide 3, alkali, ve AA216287 Hs 1815 62 19886290 452862 ADAMTS2 (a disintegπn-like and metall AW378065 Hs 8687 6 1 43608190 423575 intron of penostin (OSF-2os) C18863 Hs 163443 6 1 18206173 424078 paternally expressed 3 AB006625 Hs 139033 61 189318946225 423858 Homo sapiens mRNA, cDNA DKFZp434B0650 ( AL137326 Hs 1334836 1 18586201 416349 myomesin (M protein) 2 (165kD) X69089 Hs 79227 61 9919925556 413436 sphmgosine kinase 1 AF238083 Hs 68061 61 7217225339 449698 ESTs AA279913 Hs 31922 61 41077987 411358 KIAA1691 protein R47479 Hs 94761 61 5275186 436496 glia maturation factor, gamma AA281959 Hs 5210 61 31957199 443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 61 362136227586 431204 cytochrome c oxidase subunit Via polype F28841 Hs 250760 61 27606848 421512 myomegalin AB007923 Hs 265848 61 155415555979 432239 matrix metalloproteinase 13 (collagenas X81334 Hs 2936 61 285628576921 419846 Williams-Beuren syndrome chromosome reg NM 015977 Hs 285681 61 13895857 429490 ESTs, Weakly similar to ALU7_HUMAN ALU A1971131 Hs 23889 61 25716715 426312 interferon induced protein with tetratr AF026939 Hs 181874 61 220122026440 410223 calsequestnn 1 (fast-twitch, skeletal S73775 Hs 60708 61 4334345115 430681 ESTs AW969675 Hs 291232 60 27196819 426691 PCTAIRE protein kinase 1 NMJ06201 Hs 1 71834 60 226222636480 416047 DNA segment, numerous copies, expressed BE439894 Hs 78991 60 9655533 406664 glycerol-3 phosphate dehydrogenase 1 (s L34041 Hs 348601 60 83844819 452363 Homo sapiens, Similar lo complement com A1582743 Hs 94953 60 43228159 403087 NM_003319* Homo sapiens Win (TTN), mR 60 4706 417079 interleukin 1 receptor antagonist U65590 Hs 81134 60 107310745616 451533 serum deprivation response (phosphatidy NMJ04657 Hs 26530 60 423942408092 419138 ryanodiπe receptor 1 (skeletal) U48508 Hs 89631 60 130913105796 413773 ESTs AA131780 Hs 269925 60 7395355 427596 extracellular glycoprotein EMILIN-2 pre AA449506 Hs 270143 60 23506544 427019 hypothetical protein FLJ10970 AA001732 Hs 173233 60 22966504 438885 ESTs AI886558 Hs 184987 60 33637346 450300 ESTs, Highly similarto ITH4..HUMAN INTE AL041440 Hs 58210 59 41548024 413670 hypothetical protein, expressed in osle AB000115 Hs 75470 59 7357365352 414315 gb HSB65D052 STRATAGENE Human skeletal Z24878 59 8035409 423903 interleukin 11 M57765 Hs 1721 59 186518666206 422100 ADP-nbosylation factor-like 7 AI096988 Hs 111554 59 16446042 449579 ESTs, Weakly similar to T46425 hypothet AW207260 Hs 134014 59 40977978 421566 early growth response 2 (Krox-20 (Droso NM J00399 Hs 1 395 59 156315645984 412577 CD163 antigen Z22968 Hs 74076 59 6086095252 402507 Target Exon 58 4683 411102 triadin AA401295 Hs 23926 58 5155175 412965 procollagen-lysine, 2 oxoglutarate 5 di L06419 Hs 75093 58 6596605294 406836 immunoglobulin kappa constant AW514501 Hs 156110 58 684835 449717 cerebral cell adhesion molecule AB040935 Hs 23954 58 411041117989 431205 tropomodul 4 (muscle) AA194560 Hs 250763 58 27616B49 409103 XAGE-1 protein AF251237 Hs 112208 58 3043055021 409731 thymosm, beta, identified in neuroblas AA125985 Hs 56145 58 3865080 412471 endothelial cell growth factor 1 (plate M63193 Hs 73946 58 5915925239 427792 tumor necrosis factor receptor superfam M63928 Hs 180841 58 237123726561 419301 tenomodulm protein AA236166 Hs 132957 58 1328 5811
424440 ESTs AA340743 Hs 133208 58 1951 6266
431806 tumor necrosis factor (ligand) superfam AF186114 Hs 270737 58 282428256898
409028 Z-band alternatively spliced PDZ-motif AB014513 Hs 49998 58 2962975015
415702 gb HSPD18414 HM3 Homo sapiens cDNA clon F28877 Hs 73680 58 942 5515
406925 glyceroI-3 phosphate dehydrogenase 1 (s L34041 Hs 348601 58 83844845
409882 heat shock 27kD protein family, member AJ243191 Hs 56874 57 3953965087
412129 troponin T3, skeletal, fast M21984 Hs 73454 57 571 5725222
443595 PPAR(gamma) aπgiopoietm related protei AF169312 Hs 9613 57 362636277590
418299 integrin, beta 2 (antigen CD18 (p95), I AA279530 Hs 83968 57 1212 5725
434474 holocytochrome c synthase (cytochrome c AL042936 Hs 211571 57 3058 7084
416783 monocyte to macrophage differentiation- AA206186 Hs 79889 57 1031 5584
423057 ESTs, Moderately similar to 138022 hypo AW961597 Hs 130816 57 1773 6139
447165 Homo sapiens, Similar to RIKEN cDNA 170 AL042400 Hs 75668 57 3895 7811
415192 aldo-keto reductase family 1, member C3 D17793 Hs 78183 57 917918 5494
425003 apuπnic/apyπmidinic endonuclease(APEX AF119046 Hs 154149 57 2038 20396326
436326 aido keto reductase family 1, member B1 BE085236 Hs 42636 57 3183 7188
443623 complement component 1 , q subcomponent, AA345519 Hs 9641 57 3631 7594
422667 ESTs H25642 Hs 132821 57 1723 6102
436608 down syndrome cπtical region protein D AA628980 Hs 192371 57 3205 7207
430838 hypothetical protein FLJ12015 N46664 Hs 169395 57 2733 6829
410011 PFTAIRE protein kinase 1 AB020641 Hs 57856 56 4064075096
409253 CD5 antigen like (scavenger receptor cy H91200 Hs 52002 56 332 5041
456534 phospholipase C, beta 3, neighbor pseud X91195 Hs 100623 56 4522 8326
414531 allograft inflammatory factor 1 T69387 Hs 76364 56 829 5430
437442 ESTs, Moderately similar to similar to T85104 Hs 222779 56 3263 7258
419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 56 1381 13825851
431671 polymerase (DNA directed), alpha NM_016937 Hs 267289 56 280728086884
447232 interleukin 10 receptor, alpha AW499834 Hs 327 56 3905 7820
438707 ammo acid system N transporter 2, pore L08239 Hs 5326 56 33503351 7335
436856 ESTs AI469355 Hs 127310 56 3220 7221
451681 ESTs, Weakly similar to AA64_HUMAN 64 K Z28564 Hs 255950 56 4245 8097
444666 long chain fatty acid coeπzyme A ligase BE293347 Hs 11638 56 3712 7664
453454 PRP4/STK/WD splicing factor AW052006 Hs 374973 56 4421 8243
417678 2',5'-olιgoadenylate synthetase 1 (40-4 X06560 Hs 82396 56 1145 11465671
456508 ESTs, Weakly similar to AF208855 1 BM 0 AA502764 Hs 123469 56 4521 8325
450785 Homo sapiens, alpha-1 (VI) collagen AA852713 Hs 108885 56 4193 8056
422526 ESTs AA311763 Hs 131056 56 1695 6081
409041 Hypothetical protein, XPJJ51860 (KIAA11 AB033025 Hs 50081 56 2993005017
411127 hypothetical protein AA668995 Hs 323463 56 516 5176
430044 ESTs AA464510 Hs 152812 55 2642 6765
408122 hypothetical protein FLJ10718 A1432652 Hs 42824 55 193 4935
421779 wingless type MMTV integration site fam AI879159 Hs 108219 55 1592 6004
422726 faciogeπital dysplasia (Aarskog-Scott s U11690 Hs 1572 55 1727 1728 6106
427378 melanoma antigen, family D, 1 BE515037 Hs 177556 55 2322 6523
414561 Homo sapiens am o acid transport syste AI064813 Hs 195155 55 831 5432
422173 phorbolin-like protein MDS019 (CEM15) BE385828 Hs 250619 55 1656 6052
421369 U2 small nuclear ribonucleoprotein auxi NMJ305089 Hs 1 71909 55 1533 15345966
412170 very low density lipopratem receptor D16532 Hs 73729 55 5755765225
406722 Homo sapiens SNC73 protein (SNC73) mRNA H27498 Hs 293441 55 64 4831
409361 sine oculis homeobox (Drosophila) homol NM J05982 Hs 54416 55 3443455049
403071 NM 003319* Homo sapiens Win (TTN), mR 55 4702
420005 ESTs AW271106 Hs 133294 55 1407 5871
448988 gamma-aminobutyπc acid (GABA) A recept Y09763 Hs 22785 55 405540567940
418059 gb zn56d05 s1 Stratagene muscle 937209 AA211586 55 1186 5703
444783 aπillm (Drosophila Scraps homolog), ac AK001468 Hs 62180 55 372237237672
422106 Fc fragment of IgG binding protein D84239 Hs 111732 55 1646 16476044
433570 ESTs, Weakly similar to S55916 πbosoma AI580053 Hs 109007 55 2988 7027
426304 Homo sapiens cDNA FLJ11477 fis, clone H AA374532 Hs 124673 55 2198 6438
406387 Target Exon 55 4805
429142 ESTs AA835639 Hs 104972 55 2518 6676
453905 LIM domain kinase 1 NMJ02314 Hs 36566 55 446244638276
403362 NMJ01615* Homo sapiens actin, gamma 2, 55 4715
427557 plasminogen activator, urokinase recept NM_002659 Hs 1 79657 54 234323446539
430478 apolipoprotein L, 3 NM_014349 Hs 241535 54 270227036808
438915 Williams-Beuren syndrome chromosome reg AA280174 Hs 355711 54 3365 7348
418203 CDC28 protein kinase 2 X54942 Hs 83758 54 120212035719
452046 KIAA0802 protein AB018345 Hs 27657 54 427542768120
418532 neurotrophic tyrosine kinase, receptor, F00797 Hs 374321 54 1252 5753
414555 phospholipase A2, group HA (platelets, N98569 Hs 76422 54 830 5431
417336 disabled (Drosophila) homolog 2 (mitoge R70429 Hs 81988 54 1097 5637
427923 FGENESH predicted 11 TM protein AW274357 Hs 301406 54 2385 6572
428450 KIAA0175 gene product NMJJ14791 Hs 1 84339 54 2443 24446621
420168 serine carboxypeptidase vitellogenic-li AF217508 Hs 95594 54 1424 14255885
429134 ESTs AA446953 Hs 99004 54 2514 6673
431620 2-5'-olιgoadenyIate synthetase 2 (69-7 AA126109 Hs 264981 53 2802 6880
430233 Homo sapiens mRNA, cDNA DKFZp564N1063 ( AW367902 Hs 23644353 2664 6781
456181 ras inhibitor L36463 Hs 1030 53 451645178321
422567 glypican 6 AF111178 Hs 118407 53 1702 1703 6087
406703 myosin, heavy polypeptide 3, skeletal m X13100 Hs 173084 53 53544825
443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 53 3656 7617
427239 ubiquitin carrier protein BE270447 Hs 356512 53 2311 6515
448569 signal transducer and activator of Iran BE382657 Hs 21486 53 4014 7909
458916 ESTs N58327 Hs 302755 53 4583 8380
421848 collagen, type VI, alpha 1 X15880 Hs 108885 53 1602 16036013
406868 immunoglobulin heavy constant gamma 3 ( AA505445 Hs 300697 53 72 4839 446500 sushi repeat containing protein, X chro U78093 Hs 15154 53 384238437767
406663 immunoglobulin heavy constant mu U24683 53 39404818
422048 spondin 2, extracellular matrix protein NM_012445 Hs 288126 53 1631 16326034
435750 KIAA1089 protein AB029012 Hs 4990 53 314931507160 414459 CCAAT/enhancer binding protein (C/EBP), Y11525 Hs 76171 53 8188195422
443672 butyrobetame (gamma), 2-oxoglutarate d AA323362 Hs 9667 53 3634 7597
409512 melanoma differentiation associated pro AW979187 Hs 293591 53 354 5057
433138 semaphoπn sem2 AB029496 Hs 59729 53 294429456994
435854 putative ankyππ repeat containing prot AJ278120 Hs 4996 52 315731587166 422491 neuronatin AA338548 Hs 117546 52 1691 6077
445084 hypothetical protein FLJ14761 H38914 Hs 250848 52 3742 7687
433365 ESTs AF026944 Hs 293797 52 2973 7014
417900 CDC20 (cell division cycle 20, S cerev BE250127 Hs 82906 52 1165 5688
421064 tumor necrosis factor, alpha-induced pr AI245432 Hs 101382 52 1503 5942 416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 52 1001 10025564
433135 dolichyl-phosphatemannosyltransferase AA443873 Hs 110477 52 2943 6993
401961 NM 021626 Homo sapiens serine carboxype 52 4669
433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 52 292329246977
424090 XIAP associated factor-1 X99699 Hs 139262 52 189718986228 436252 Homo sapiens CDNA FLJ11562 fis, clone H A1539519 Hs 142827 52 3179 7184
443898 Sec61 gamma AW804296 Hs 9950 52 3655 7616
445584 PTD012 protein AF217518 Hs 8360 52 378637877719
421778 actin related protein 2/3 complex, subu AA428000 Hs 283072 52 1591 6003
422481 DNAX-activation protein 10 AL050163 Hs 117339 52 168716886075 442619 ESTs, Weakly similar to AF164793 1 prot AA447492 Hs 20183 52 3575 7545
419405 ESTs AI377043 Hs 42189 52 1333 5816
445107 ESTs, Weakly similar to I38022 hypothet A1208121 Hs 147313 52 3744 7689
434096 pleiomorphic adenoma gene like 1 AW662958 Hs 75825 52 3029 7062
416982 creatine kinase, mitochondπal 2 (sarco J05401 Hs 80691 52 105510565602 439926 ESTs AW014875 Hs 137007 52 3440 7422
435680 Homo sapiens galectin-related inhibitor H50946 Hs 84183 52 3145 7157
421155 lysyl oxidase H87879 Hs 102267 52 1512 5950
457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs 32399 52 4543 8344
412473 ESTs F23393 Hs 153060 52 594 5241 438086 πuclearreceptorεubfamily 1, group I, AA336519 Hs 83623 52 3300 7293
431103 pleiotrophin (hepann binding growth fa M57399 Hs 44 52 274827496840
413350 t complex-associated-testis expressed 1 U02556 Hs 75307 52 7047055328
450506 fibroblast activation protein, alpha NMJ04460 Hs 418 52 41704171 8037
449118 Bet1 (S cerevisiae) homolog R67477 Hs 23103 52 4065 7949 418072 Human DNA sequence from clone RP3-353C1 F35210 Hs 86507 52 1190 5707
428227 small inducible cytokine subfamily B (C AA321649 Hs 2248 51 2410 6593
434868 collagen, type VI, alpha 2 R50032 Hs 159263 5 1 3085 7106
424982 phosphorylase, glycogen, muscle (McArdl U94777 Hs 351580 51 203620376325
443883 serine (or cysteme) proteinase inhibit AA114212 Hs 9930 5 1 3653 7614 427527 immunoglobulin heavy constant mu AI809057 Hs 153261 51 2340 6536
414695 proteasome (prosome, macropaiπ) subunit BE439915 Hs 76913 5 1 850 5446
441783 Homo sapiens clone 25012 mRNA sequence BE313412 Hs 7961 51 3537 7509
436748 collagen, type VI, alpha 2 BE159107 Hs 159263 5 1 3212 7213
444186 ESTs AI127666 Hs 146447 51 3685 7642 452056 Homo sapiens, clone IMAGE 4054156, mRNA AW955065 Hs 10115051 4280 8123
429997 apolipoprotein B mRNA editing enzyme, c NM_006789 Hs 227457 51 263626376761
433048 ESTs, Weakly similar to ALU8_HUMAN ALU R91007 Hs 194116 5 1 2932 6984
410889 twist (Drosophila) homolog (acrocephalo X91662 Hs 66744 5 1 501 5025164
414020 small inducible cytokine A4 (homologous NM 002984 Hs 75703 51 7677685378 431241 ESTs AA496799 Hs 36958 51 2765 6852
421458 carbohydrate (keratan sulfate Gal-6) su NMJ03654 Hs 1 04576 51 154315445972
416586 secreted modular calcium binding protei D44643 Hs 14144 51 1016 5574
412006 ESTs AW451618 Hs 380683 5 1 565 5217
418452 C-type (calcium dependent carbohydrate BE379749 Hs 85201 51 1241 5744 430252 testes development-related NYD SP20 AI638774 Hs 105328 51 2668 6784
415672 ESTs N53097 Hs 193579 51 937 5511
429415 procollagen C-endopeptidase enhancer NM_002593 Hs 202097 51 255725586706
443780 activating transcription factor 5 NM_012068 Hs 9754 51 364336447606
418322 cyclin dependent kinase inhibitor 3 (CD AA284166 Hs 84113 50 1214 5727 416433 ESTs AI658904 Hs 84673 50 1004 5566
448694 E3 ubrquitin ligase SMURF2 AA478756 Hs 194477 50 4027 7919
407172 gb ya92c05 s1 Stratagene placenta (9372 T54095 Hs 379019 50 117 4869
433446 ESTs AW469546 Hs 122116 50 2979 7020
446157 Homo sapiens cDNA FLJ22562 fis, clone BE270828 Hs 131740 50 3821 7749 447343 ESTs, Highly similar to S02392 alpha-2- AA256641 Hs 236894 50 3916 7828
427051 Homo sapiens CDNA FLJ10500 fis, clone N BE178110 Hs 173374 50 2297 6505
440087 hypothetical protein FLJ22678 W28969 Hs 7718 50 3452 7433
425825 lymphocyte antigen 6 complex, locus H AI929508 Hs 159590 50 2147 6399
425843 death associated protein 3 BE313280 Hs 159627 50 2149 6401 426968 amphiphysin (Stiff-Mann syndrome with b U07616 Hs 173034 50 22902291 6499
441020 ESTs W79283 Hs 35962 50 3495 7471
411894 GU-Kruppel family member GLI3 (Greig c M57609 Hs 72916 50 5595605212
436222 Homo sapiens cDNA FLJ 11489 fis, clone H AI208737 Hs 122810 50 3177 7182
416431 Win AW384459 Hs 172004 50 1003 5565 445417 a disintegπn-like and metalloprotease AK001058 Hs 12680 50 3766 7705
424291 ephπn-B1 AL120051 Hs 144700 50 1931 6249
413186 solute carrier family 16 (monocarboxyli AU077141 Hs 75231 50 685 5315
410600 ESTs, Moderately similar to S65657 alph AW575742 Hs 351676 50 479 5147
425514 integrin, alpha 10 AF112345 Hε 158237 50 210821096375 431385 membrane-spanning 4-domaιns, subfamily BE178536 Hs 11090 50 2779 6863
432485 CDW52 antigen (CAMPATH-1 antigen) N90866 Hs 276770 50 2877 6939 438158 ESTs AI796556 Hs 187884 50 33057298 425398 hypothetical protein similar to tenasci AL049689 Hs 156369 50 210121026370 406621 immunoglobulin lambda locus X57809 Hs 181125 50 26274810 421483 hypothetical protein MGC11333 NM 003388 Hs 1 04717 50 154515465973 450701 hypothetical protein XPJ98151 (leucine H39960 Hs 288467 50 41838048 441188 ESTs AW292830 Hs 255609 50 35037478 408989 KIAA0746 protein AW361666 Hs 49500 50 2905010 439867 ESTs AA847510 Hs 161292 50 34357418 410867 fibnllin 1 (Marfan syndrome) X63556 Hs 750 50 4984995162 403086 NM 03319* Homo sapiens titin (TTN), mR 50 4705 419726 bone morphogenetic protein 1 U50330 Hs 1274 49 137613775848 448807 ESTs AI571940 Hs 7549 49 40417930 425708 hypothetical protein FLJ22530 AK001342 Hs 14570 49 212821296388 452438 JM4 protein BE514230 Hs 29595 49 43318165 409649 hypothetical protein FLJ20442 AA159216 Hs 55505 49 3735070 430009 ESTs AA894564 Hs 22242 49 26386762 417640 protein C receptor, endothelial (EPCR) D30857 Hs 82353 49 11435669 452106 ESTs AI141031 Hs 21342 49 42898131 415701 gamma-glutamyl hydrolase (conjugase, fo NM J03878 Hs 78619 49 9409415514 428242 leukemia inhibitory factor (cholinergic H55709 Hs 2250 49 2411 6594 424623 ESTs AW963062 Hs 270737 49 19776282 422609 sialidase 1 (lysosomal sialidase) Z46023 Hs 118721 49 1711 6093 444476 isocitrate dehydrogenase 1 (NADP). solu AF020038 Hs 11223 49 370137027656 417511 chordiπ-like AL049176 Hs 82223 49 112511265657 429044 ESTs AI261490 Hs 145527 49 25066667 441362 RAD51 (S cerevisiae) homolog (E coli R BE614410 Hs 23044 49 35127486 438203 ESTs BE540090 Hs 7345 49 33087300 416737 LIM domain protein AF154335 Hs 79691 49 102810295582 449318 Homo sapiens, Similar to RIKEN cDNA 573 AW236021 Hs 78531 49 40807962 450390 Human DNA sequence from clone RP11-234G N93227 Hs 348805 49 41638031 410701 RNA binding motif protein 8A AF198620 Hs 10283 49 4874885154 422867 cartilage oligomeric matrix protein (ps L32137 Hs 1584 49 175117526122 439981 ESTs, Weakly similar to T14742 hypothet AI348408 Hs 124675 49 34437425 427399 KIAA0914 gene product NM_014883 Hs 1 77664 49 232323246524 421395 pyruvate dehydrogenase (lipoamide) alph D90084 Hs 1023 49 153815395969 438441 ESTs AW664960 Hs 205319 49 33227312 416404 ESTs AA180138 Hs 107924 49 10005563 447297 protease, cysteme, 1 (legumain) BE617970 Hs 18069 49 39147826 427209 KIAA1566 protein H06509 Hs 92423 49 23096513 406646 major histocompalibility complex, class M33600 Hs 375570 48 36374816 415076 guanylate cyclase 1, soluble, beta 3 NM 000857 Hs 77890 48 9069075486 421143 immunoglobulin superfamily containing I AB024536 Hs 102171 48 151015115949 423750 prefoldm 2 AF165883 Hs 298229 48 184318446191 423732 solute carrier family 16 (monocarboxyli AF058056 Hs 132183 48 184018416189 408482 adenosine A2b receptor NM 000676 Hs 45743 48 2262274959 439688 hypothetical protein FLJ12921 AW445181 Hs 209637 48 34187401 431070 transcription factor 19 (SC1) AW408164 Hs 249184 48 27446837 426935 collagen, type I, alpha ' NMJ00088 Hs 1 72928 48 228822896498 417011 ESTs, Weakly similar to 2109260A B cell F08212 Hs 234898 48 10605605 413945 CD 14 antigen NMJ00591 HS 75627 48 7587595371 418205 troponin I, skeletal, fast L21715 Hs 83760 48 120412055720 432211 hypothetical protein FLJ10986 BE274530 Hs 273333 48 28526917 440086 v-ral simian leukemia viral oncogene ho NM 005402 Hs 6906 48 345034517432 408901 hypothetical protein FLJ10468 AK001330 Hs 48855 48 2722734997 443021 lg superfamily protein AA368546 Hs 8904 48 35937561 431801 Homo sapiens cDNA FLJ10302 fis, clone N A1907522 Hs 270555 48 28236897 414600 traπsducm (beta)-lιke 1 NM..005647 Hs 76536 48 8358365436 408380 diubiquitin AF123050 Hs 44532 48 2172184952 402621 Target Exon 48 4684 424755 KIAA1268 protein AB033094 Hs 152925 48 199519966295 409485 ficolm (collageπ/fibrinogen domain con S80990 Hs 252136 48 3513525055 421362 hypothetical protein FLJ20043 AK000050 Hs 103853 48 153115325965 445537 EGF-like domain, multiple 6 AJ245671 Hs 12844 48 378037817716 433819 ESTs AW511097 Hs 110069 48 30077042 425280 phosphoenolpyruvate carboxykmase 1 (so U31519 Hs 1872 48 208020816357 427498 methyl-CpG binding domain protein 3 NMJ03926 Hs 1 78728 48 233623376534 444931 general transcription factor IIIA AV652066 Hs 75113 48 37357681 450000 hypothetical protein FLJ21709 AI952797 Hs 10888 48 41268003 425776 parathyroid hormone receptor 2 U25128 Hs 159499 48 213821396394 412755 ESTs, Weakly similar to P4HA HUMAN PROL BE144306 Hs 17989148 6375274 445043 ESTs AW014413 Hs 196066 48 37417686 407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 48 1664910 418918 CD2 antigen (p50), sheep red blood cell X07871 Hs 89476 48 128212835775 435080 hypothetical protein FLJ14428 AI831760 Hs 155111 48 31037122 423225 Thy-1 cell surface antigen AA852604 Hs 125359 48 17866148 453985 ESTs N44545 Hs 251865 48 44778287 417849 nidogen 2 AW291587 Hs 82733 48 1161 5684 430441 desmoplakin (DPI, DPII) BE398091 Hs 374850 48 26996805 417621 interferoπ-induced, hepatitis C-associa AV654694 Hs 82316 48 11405666 431183 KDEL (Lys-Asp Glu Leu) endoplasmic reti NM J06855 Hs 250696 48 275627576845 402408 NMJ30920* Homo sapiens hypothetical pr 48 4681 408024 ESTs AW905599 Hs 171501 48 1864928 414313 coato er protein complex, subunit alpha NMJ04371 Hs 75887 47 8018025408 420059 RAB23, member RAS oncogene family AF161486 Hs 94769 47 141214135875 406636 gb Homo sapiens (clone WR4 12VL) and t L12064 47 32334814 445434 hypothetical protein FLJ20917 BE391690 Hs 9265 47 37697707 411962 gb zk85d12 r1 Soares_pregnant_uterus_Nb AA099050 47 563 5215
417166 Paired box protein Pax-3 AA431323 Hs 42146 47 1088 5628
441187 hypothetical protein FLJ22174 AW195237 Hs 7734 47 3502 7477
432878 Pinn BE386490 Hs 279663 47 2914 6969
435554 early B cell factor AF208502 Hs 32425 47 313631377150
456804 caveolιn 2 AI421645 Hs 139851 47 4529 8332
446035 Sam68-lιke phosphotyrosme protein, T-S NM_006558 Hs 1 3565 47 381338147742
435099 flap structure specific endonuclease 1 AC004770 Hs 4756 47 310431057123
407903 bHLH factor Hes4 AI287341 Hs 154029 47 178 4920
407204 ESTs, Weakly similar to ALU1_HUMAN ALU R41933 Hs 140237 47 121 4873
452613 ESTs AA461599 Hs 23459 47 4337 8171
431347 insulin like growth factor 2 (somatomed AI133461 Hs 251664 47 2774 6859
447660 ESTs AW160386 Hs 163667 47 3946 7853
433036 ESTs AA574091 Hs 105964 47 2929 6981
453828 ESTs AW970960 Hs 293821 47 4444 8262
417767 acyloxyacyl hydrolase (neutrophil) BE242241 Hs 82542 47 1155 5678
454024 hypothetical protein FLJ23403 AA993527 Hs 293907 47 4481 8290
422809 hypothetical protein FLJ10549 AK001379 Hs 121028 47 1741 17426115
458208 ESTs, Weakly similarto T4S4J.UMAN TRAN AI380016 Hs 352394 47 4570 8367
416391 mesoderm specific transcript (mouse) ho AI878927 Hs 79284 47 999 5562
448030 membrane-spanning 4-domaιns, subfamily N30714 Hs 325960 47 3971 7873
414166 N-myc downstream regulated AW888941 Hs 75789 47 784 5392
422477 ankyπn repeat domain 2 (stretch respoπ AA345800 Hs 73708 47 1686 6074
417376 LIM protein (similar to rat protein km AA253314 Hs 154103 47 1107 5645
405259 C12000526* gι|7512168|pιr]|T30886 integ 47 4774
431706 adenylyl cyclase-associated protein 2 AI816086 Hs 296341 47 2811 6887
437802 ESTs AI475995 Hs 122910 47 3288 7281
412749 signal sequence receptor, beta (translo AA378417 Hs 74564 47 635 5272
435370 ESTs AI964074 Hs 225838 47 3120 7136
404977 Insulin like growth factor 2 (somatomed 47 4766
433264 cysteine dioxygenase, type I D85782 Hs 3229 47 2965 29667007
400528 NM-.020975* Homo sapiens ret proto-oncog 47 4631
406707 myosin, heavy polypeptide 2, skeletal m S73840 Hs 931 46 61 624829
428405 cholmergic receptor, nicotimc, alpha Y00762 Hs 2266 46 243624376615
422424 prostate differentiation factor AI186431 Hs 296638 46 1681 6070
426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 46 2219 6453
414694 HSPC002 protein NM_015362 Hs 76907 46 8488495445
412490 Homo sapiens cDNA FLJ22528 fis, clone AW803564 Hs 288850 46 595 5242
415812 TATA box binding protein (TBP)-assocιat AA077268 Hs 78865 46 949 5521
429930 ESTs AI580809 Hs 352364 46 2623 6751
407252 ESTs AA659037 Hs 163780 46 134 4882
426272 ESTs AW450671 Hs 88012 46 2191 6434
406627 ESTs T64904 Hs 163780 46 30 4812
454029 homeo boxA5 W05150 Hs 37034 46 4482 8291
414004 ESTs Moderately similar to 2115357A TY AA737033 Hs 7155 46 765 5376
429380 secretory carrier membrane protein 3 AF023268 Hs 200600 46 255425556704
428291 interferon stimulated gene (20kD) AA534009 Hs 183487 46 2423 6604
402855 NM_001839* Homo sapiens calponm 3, aci 46 4694
418140 microfibrillar-associated protein 2 BE613836 Hs 83551 46 1196 5713
400297 hypothetical protein DKFZp56401278 AI127076 Hs 288381 46 7 4618
414416 hypothetical protein MGC2721 AW409985 Hs 76084 46 813 5417
424876 Homo sapiens clone IMAGE 297403, mRNA s A1056991 Hs 269873 46 2016 6310
419250 U5 snRNP-specific protein, 116 kD AW770185 Hs 356066 46 1322 5806
458207 U2 small nuclear nbonucleoprotein auxi T28472 Hs 7655 46 4569 8366
445930 Homo sapiens clone 24747 mRNA sequence AF055009 Hs 13456 46 3804 7734
411027 leukocyte immunoglobulin like receptor, AF072099 Hs 67846 46 5095105170
414809 transferπn receptor (p90, CD71) A1434699 Hs 77356 46 873 5463
419407 hypothetical protein FLJ21276 AW410377 Hs 41502 46 1334 5817
431231 ESTs AA653552 Hs 116532 46 2764 6851
438451 ESTs AI081972 Hs 220261 46 3323 7313
417750 synovial sarcoma, translocated to X chr AI267720 Hs 260523 46 1154 5677
407930 Homo sapiens cDNA FLJ12807 fis, clone N AA045847 Hs 188361 46 182 4924
410738 Win AA197128 Hs 172004 46 491 5156
422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 46 1734 6110
436802 ESTs N34486 Hs 132183 46 3216 7217
437669 ESTs, Weakly similar to match to ESTs A AI358105 Hs 123164 46 3278 7271
416658 fibπllin 2 (congenital contractural ar U03272 Hs 79432 46 1020 1021 5577
432290 Homo sapiens cDNA FLJ10237 fis, clone H AK001099 Hs 274273 46 2862 6926
453767 extracellular matrix protein 2, female AB011792 Hs 35094 46 443944408258
424651 ESTs AI493206 Hs 120785 46 1984 6287
421016 transcπption factor 3 (E2A immunoglobu AA504583 Hs 101047 45 1497 5937
435460 ESTs AA682439 Hs 118380 45 3126 7142
449353 ESTs AA001220 Hs 242947 45 4084 7966
413441 Src-like-adapter AI929374 Hs 75367 45 723 5340
425568 ESTs AW963118 Hs 161784 45 2115 6380
433614 cytochrome c oxidase subunit IV isoform W07475 Hs 277101 45 2993 7031
427600 proteasome (prosome, macropain) activat AW630918 Hs 179774 45 2351 6545
444638 ESTs AI445775 Hs 143806 45 3709 7661
417352 gb zp95h09 r1 Stratagene muscle 937209 AA195919 Hs 86045 45 1099 5639
413943 Homo sapiens cDNA FLJ12981 fis, clone N AW294416 Hs 144687 45 757 5370
439332 Homo sapiens mRNA, cDNA DKFZp547M072 (f AW842747 Hs 378821 45 3393 7376
452052 midline 1 (Opitz/BBB syndrome) NM 100381 Hs 27695 45 427742788121
410817 protein disulfide isomerase related pro AI262789 Hs 93659 45 497 5161
444842 bromodomain adjacent to zinc finger dom AF084479 Hs 194688 45 372937307676
400419 Target AF084545 45 22234626
417920 adenosine monophosphate deaminase 2 (is S47833 Hs 82927 45 1167 11685690 408964 beta site APP cleaving enzyme AF201468 Hs 49349 45 2842855006 439453 thyroid hormone receptor interactor 13 BE264974 Hs 6566 45 33997382 408212 hypothetical protein AA297567 Hs 43728 45 2064945 443142 protein phosphatase 2 (formerly 2A), re AI696513 Hs 108705 45 36047571 452063 ESTs, Weakly similar to TWST_HUMAN TWIS R53185 Hs 32366 45 42818124 439815 hypothetical protein FLJ20420 AA206079 Hs 6693 45 34337416 403074 NM_003319* Homo sapiens Win (TTN), mR 45 4703 447898 62 kd protein AW969638 Hs 380920 45 39667868 431757 Homo sapiens chromosome 21q22 1 anonymo AA196930 Hs 26852645 28176892 426822 ESTs W78950 Hs 220823 45 22776489 424001 paternally expressed 10 W67883 Hs 137476 45 18826217 414178 ESTs, Weakly similar to I38022 hypothet AW957372 Hs 46791 45 7885396 414862 single-stranded DNA-bindmg protein BE621310 Hs 923 45 8825468 443960 hypothetical protein FLJ21986 AI093577 Hs 255416 45 36637623 427458 ESTs, Weakly similar to LKHU proteoglyc BE208364 Hs 29283 45 23326530 418867 msh (Drosophila) homeo box homolog 2 D31771 Hs 89404 45 127712785772 415656 ESTs W84346 Hs 84673 45 9335507 447484 hypothetical protein FLJ 14697 AA464839 Hs 292566 45 39337841 435373 ESTs AW665538 Hs 117689 45 31217137 424834 Homo sapiens cDNA FLJ10570 fis, clone N AK001432 Hs 153408 45 20096304 439731 hypothetical protein FLJ14084 AI953135 Hs 45140 45 34257408 453859 myogeπic factor 6 (herculm) NMJ02469 Hs 35937 45 445144528267 431104 ESTs AW970859 Hs 313503 45 27506841 452698 chemokme (C-C motif) receptor 1 NM 001295 H s 301921 45 434343448177 414883 CDC28 protein kinase 1 AA926960 Hs 348669 45 8855471 409197 chromosome 11 open reading frame 24 N54706 Hs 303025 45 3225035 412974 emopamil binding protein (sterol isomer R18978 Hs 75105 45 6645297 430770 ESTs AA765694 Hs 123296 45 27276825 444681 chromosome 6 open reading frame 9 AJ243937 Hs 288316 44 371537167667 447463 Mitochoπdπal Acyl-CoA Thioesterase AW378685 Hs 18625 44 39297838 428281 ATPase, H transporting, lysosomal (vacu AA194554 Hs 183434 44 24196601 408866 ESTs AW292096 Hs 255036 44 2704995 449175 homolog of yeast SPB1 AJ005892 Hs 23170 44 406840697952 444669 ESTs F18939 Hs 153827 44 37137665 431093 eomesodermm (Xenopus laevis) homolog AB031038 Hs 301704 44 274627476839 412448 tumor necrosis factor receptor superfam L12964 Hs 73895 44 5875885236 444385 CGI-111 protein BE278964 Hs 11085 44 36987653 423595 ESTs R82826 Hs 220702 44 18236176 457567 gb QV1-DT0069 010200 057 d 2 DT0069 Hom AW939074 44 45578355 407896 Zic family member 1 (odd-paired Drosoph D76435 Hs 41154 44 1761774919 451938 down reg ulator of transcription 1 , TBP- AI354355 Hs 16697 44 42638110 432680 interferon, alpha inducible protein 27 T47364 Hs 278613 44 28956954 428795 ESTs, Highly similar to A39769 N-acetyl R45503 Hs 97469 44 24756643 407907 pracollagen lysine, 2-oxoglutarate 5 di AI752235 Hs 41270 44 1794921 440184 dedicator of cyto kinesis 3 AB002297 Hs 7022 44 345934607439 452664 hypothetical protein FLJ23221 AA398859 Hs 18397 44 43398173 445893 ESTs, Weakly similar to TRHY_HUMA TRICAI610702 Hs 202613 44 38027732 412430 fumarylacetoacetate hydrolase (fumaryla AW675064 Hs 73875 44 5845233 452203 transporter 1 , ATP-bmdiπg cassette. su X57522 Hs 352018 44 429842998140 441224 calumenm AU076964 Hs 7753 44 35047479 436519 myozenin AJ278124 Hs 238756 44 319631977200 439265 Homo sapiens cDNA FLJ23197 fis, clone AL134430 Hs 6906 44 33887371 428048 gb zf41b11 s1 Soares_fetal_heart_NbHH19 AA705745 44 23946580 414653 procollageπ-proline 2-oxoglutarate 4-d M24486 Hs 76768 44 8418425441 408787 Rho guanine exchange factor (GEF) 11 NMJM4784 Hs 47822 44 2582594987 406672 major histocompatibility complex, class M26041 Hs 198253 44 43444820 403291 Target Exon 44 4713 422624 KDEL (Lys-Asp-Glu-Leu) endoplasmic reti BE616678 Hs 380986 44 17146096 459531 hypothetical protein FLJ11500 similar t AI200996 Hs 148533 44 45948390 412014 ESTs Weakly similar to A46010 X-lιnked AI620650 Hs 43761 44 5665218 451186 ESTs, Weakly similar to leucine-nch gl AW023469 Hs 65256 44 42178076 439302 ESTs AW467516 Hs 208109 44 33907373 407103 hypothetical protein MGC13170 AA424881 Hs 256301 44 1104862 429052 ESTs AA443938 Hs 368387 44 25096669 407754 Homo sapiens cDNA FLJ14105 fis, clone M AA527348 Hs 288967 44 158 4902 408365 hypothetical protein FLJ20514 AK000521 Hs 44423 44 2142154950 410079 glycogeniπ 2 U94362 Hs 380757 44 4184195104 421893 vascular cell adhesion molecule 1 NM_001078 Hs 1 09225 44 1608 1609 6018 407241 gb Human omega light chain protein 14 1 M34516 44 130 131 4880 414283 ESTs AW960011 Hs 154993 43 797 5404 453817 ESTs AW755253 Hs 379636 43 4442 8260 444969 ESTs AI203334 Hs 171862 43 3736 7682 423600 ESTs AI633559 Hs 310359 43 1824 6177 415169 ATPase, vacuolar, 14 kD W42913 Hs78089 43 915 5492 407756 ubiquitin specific protease 18 AA116021 Hs 38260 43 1594903 456115 Win F01082 Hs 172004 43 45158320 422241 protein tyrosine phosphatase, receptor Y00062 Hs 170121 43 166316646058 443639 proteasome (prosome, macropain) subunit BE269042 Hs 9661 43 36327595 448258 hypothetical protein FLJ20396 BE386983 Hs 343214 43 39907889 424218 cystatin F (leukocystatin) AF031824 Hs 143212 43 191319146239 426283 kynurenmase (L-kynurenine hydrolase) NMJ03937 Hs 169139 43 219221936435 438568 major histocompatibility complex, class R98865 Hs 11135 43 33367324 411000 ESTs, Weakly similar to S38383 SEB4B pr N40449 Hs 201619 43 5055167 429351 hypothetical protein FLJ10628 AK001490 Hs 200016 43 254925506701 448019 ESTs, Moderately similar to 138022 hypo AW947164 Hs 195641 43 39707872 410006 eukaryotic translation initiation facto AW732308 Hs 57783 43 4055095 412359 gb QV3-LT0048-140200-083 e05 LT0048 Hom AW837985 Hs 56729 43 5835232 427871 Homo sapiens, clone IMAGE 3507281, mRNA AW992405 Hs 35240643 23806568 433757 ESTs AI949974 Hs 152670 43 30027038 429455 CD209 antigen AI472111 Hs 278694 43 25636710 442426 hypothetical protein MGC5370 AI373062 Hs 332938 43 35627534 415512 paralemmin Y16270 Hs 78482 43 9299305504 428618 Target CAT AA885360 Hs 351796 43 24566629 402685 Target Exon 43 4687 424192 P311 protein U30521 Hs 142827 43 191119126238 417911 chaperonin containing TCP1, subunit 6A AA333387 Hs 82916 43 11665689 428125 leucine aminopeptidase AA393071 Hs 182579 43 24006585 446742 putative G-protein coupled receptor AA232119 Hs 16085 43 38707790 453862 Homo sapiens mRNA, cDNA DKFZp434B1231 ( AL137493 Hs 35945 43 445344548268 409267 traπsducm (beta)-lιke 2 NM_012453 Hs 52515 43 3373385044 411149 ESTs N68715 Hs 269128 43 5175177 449194 ESTs R43799 Hs 23783 43 40707953 436827 guanine nucleotide binding protein (G p H72187 Hs 356668 43 32187219 447178 ESTs AW594641 Hs 192417 43 38967812 422801 nuclear receptor co repressor 2 AF125672 Hs 287994 43 173917406114 426156 natnuretic peptide receptor A/guanylat BE244537 Hs 167382 43 21836427 436895 carbonic anhydrase XII AF037335 Hs 5338 43 322432257224 413328 guanylate cyclase 1, soluble, alpha 3 Y15723 Hs 75295 43 7017025326 426108 programmed cell death 5 AA622037 Hs 166468 43 21736420 432503 ESTs AA551196 Hs 188952 43 28786940 428342 Homo sapiens cDNA FLJ13458 fis, clone P AI739168 Hs 349283 43 24326611 408864 excision repair cross complementing rod AA521132 Hs 48576 43 2694994 407868 proline rich Gla (G-carboxyglutamic aci NM 000950 Hs 40637 43 1721734916 420261 fibroblast growth factor receptor 1 (fm AW206093 Hs748 43 14405897 426858 ubiquitously-expressed transcript NMJ04182 Hs 1 72791 43 228022816492 412520 H2A histone family, member O AA442324 Hs 795 43 5995245 429228 ESTs AI553633 Hs 356828 43 25336687 444670 hypothetical protein MGC5370 H58373 Hs 332938 43 37147666 421873 chromosome 14 open reading frame 2 AI132988 Hs 109052 43 16056015 436962 DKFZP564I052 protein AW377314 Hs 5364 43 32297228 452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 43 431043118150 425071 deiodinase, lodothyronme, type II NM_013989 Hs 1 54424 43 204320446330 419050 adenosine monophosphate deaminase 1 (is NM_000036 Hs 89570 43 129312945784 414285 ESTs AA312914 Hs 71719 43 7985405 452277 KIAA1223 protein AL049013 Hs 28783 43 43088148 418457 Deleted in split-hand/split-foot 1 regi N95406 Hs 333495 43 12425745 430683 Homo sapiens PAC clone RP4-697H17from AC004862 43 27206820 442376 Homo sapiens cDNA FLJ12228 fis, clone M W95588 Hs 129982 43 35577529 412805 Homo sapiens, Similar to bromodomain co AW954569 Hs 278675 42 6475283 421225 MCT-1 protein AA463798 Hs 102696 42 15175954 417045 Homo sapiens ORF1 F01180 Hs 332030 42 10665610 412856 basigin (OK blood group) BE386745 Hs 74631 42 6525287 400517 leπgsin 42 4630 414031 hypothetical protein MGC10848 W22615 Hs 207443 42 7705380 452960 protein tyrosine phosphatase, receptor AK001335 Hs 31137 42 43738201 418741 ESTs, Weakly similar to S41044 chromoso H83265 Hs 8881 42 12725767 410512 hypothetical protein MGC3180 AA085603 Hs 250570 42 4685140 414260 K1AA0218 gene product NM 014760 Hs 75863 42 7937945401 caspase recruitment domain protein 6 AW196663 Hs 200242 42 40497935
438596 ESTs AA829427 Hs 243081 42 33377325 424321 lymphocyte-specific protein tyrosine ki W74048 Hs 1765 42 19336251 444172 ESTs, Moderately similar to I38022 hypo BE147740 Hs 279789 42 36847641 409703 2'-5'-olιgoadenylate synthetase 3 (100 NMJ06187 Hs 56009 42 3813825076 442432 hypothetical protein FLJ23468 BE093589 Hs 38178 42 35637535 409556 phosphorylase kinase, alpha 2 (liver) D38616 Hs 54941 42 3613625061 400991 Target Exon 42 4641 411252 MD-2 protein AB018549 Hs 69328 42 5215225181 452260 RAB9, member RAS oncogene family AA453208 Hs 330994 42 43078147 420311 Human DNA sequence from clone RP4-530I1 AW445044 Hs 38207 42 14445901 435101 ESTs AI743156 Hs 131064 42 31067124 406519 C10001858 gι|6679124|ref|NP_032759 1| n 42 4808 414522 Immunoglobulin J chain AW518944 Hs 76325 42 8275428 432692 ESTs AW974944 Hs 285814 42 28996957 446291 interferon, gamma inducible protein 30 BE397753 Hs 14623 42 38337760 414747 centromere protein F (350/400kD, mitosi U30872 Hs 77204 42 8618625455 424494 phosphatιdyiιnosιtol-4-phosphate 5 kina U78575 Hs 149255 42 196119626273 453000 retiπoblastoma binding protein 7 AW411340 Hs 31314 42 43788206 448771 SNARE protein BE315511 Hs 296244 42 40347925 415938 A kinase (PRKA) anchor protein 1 BE383507 Hs 78921 42 9595528 450423 sialoadhes AA486735 Hs 31869 42 41678035 414915 myxovirus (influenza) resistance 1, hom NMJ02462 Hs 76391 42 8888895473 416804 spondyloepiphyseal dysplasia, late NMJ14563 Hs 1 74038 42 103310345586 441283 ESTs AA927670 Hs 131704 42 35067481 435232 cyclm dependent kinase inhibitor 2C (p NMJ01262 Hs 4854 42 311431157132 450923 ESTs AW043951 Hs 38449 42 42038063 458806 Homo sapiens PNAS-13 mRNA, complete eds BE514753 Hs 292057 42 45808377 424880 retinitis pigmentosa GTPase regulator NMJ300328 Hs 1 53614 4 2 201820196312 413384 exostoses (multiple) 2 NMJ00401 Hs 75334 42 7087095330 427274 colony stimulating factor 1 receptor, f NM_005211 Hs 1 74142 42 231323146517 439039 ESTs AI656707 Hs 48713 42 33737356 429803 RAB31, member RAS oncogene family W81489 Hs 223025 42 26126743 417675 similar to murine leucine-nch repeat p Hs 3781 42 11445670 416330 galactosidase, beta 1 AU077101 Hs 79222 42 990 5555
451806 RNA 3 -terminal phosphate cyclase NM..003729 Hs 27076 42 425742588105
452401 tumor necrosis factor, alpha induced pr NM 007115 Hs 29352 42 432543268161
443462 ESTs AI064690 Hs 171176 42 3623 7587 414907 polo (Drosophιa)-lιke kinase X90725 Hs 77597 42 8868875472
412642 hepatocyte growth factor (hepapoietin A BE244598 Hs 809 42 622 5261
431882 engrailed homolog 1 NMJ01426 Hs 271977 42 283228336903
413833 centromere protein E (312kD) 215005 Hs 75573 42 7487495363
413048 mannose receptor, C type 1 M93221 Hs 75182 42 6726735305 434883 hypothetical protein MGC12959 AW381538 Hs 19807 42 3088 7108
41 878 ADP-πbosylation factor 5 AA341040 Hs 77541 42 884 5470
452240 ESTs A1591147 Hs 61232 42 4304 8144
416322 pyrrolιne-5 carboxylate reductase 1 BE019494 Hs79217 42 989 5554
413004 interleukin enhancer binding factor 2, T35901 Hs75117 42 667 5300 432435 ESTs BE218886 Hs 282070 42 2874 6936
421485 hypothetical protein FLJ10134 AA243499 Hs 104800 42 1547 5974
418197 gb zn58g02 r1 Stratagene muscle 937209 AA214253 Hs 50794 41 1200 5717
420238 ESTs, Weakly similar to 2109260A B cell AA256783 Hs 12549 41 1436 5894
437275 ESTs, Weakly similar to A47582 B cell g AW976035 Hs 292396 41 3251 7248 441406 phosphoprotein regulated by mitogenic p Z45957 Hs7837 41 3518 7491
446272 hematopoietic cell-specific Lyn substra BE268912 Hs 14601 41 3832 7759
433230 ESTs AW136134 Hs 220277 41 2960 7004
430522 KIAA0471 gene product N75750 Hs 242271 41 2706 6810
427954 metaxin l J03060 Hs 247551 41 2387 6574 434974 eukaryotic translation initiation facto AA778711 Hs 362973 41 3094 7113
439223 UL16 binding protein 2 AW238299 Hs 250618 41 3383 7366
448111 interferon induced protein with tetratr AA053486 Hs 20315 41 3978 7880
452012 kmesin family member 4A AA307703 Hs 279766 41 4269 8116
429623 G protein coupled receptor kinase 5 NM 005308 Hs 211569 41 2591 25926729 433839 ESTs, Weakly similar to ALU1_HUMAN ALU F35430 Hs 146070 41 3008 7043
451514 beta-1 ,3 glucuronyltransferase 3 (glucu NM_012200 Hs 26492 41 423742388091
425797 platelet activating receptor homolog AF002986 Hs 159545 41 214221436396
427747 seπne/threonine kinase 12 AW411425 Hs 180655 41 2365 6557
438866 tissue inhibitor of metalloproteinase 2 U44385 Hs 6441 41 33603361 7344 409461 N myc (and STAT) interactor AA382169 Hs 54483 41 350 5054
444371 forkhead box M1 BE540274 Hs 239 41 3696 7651
419081 ESTs AI798863 Hs 87191 41 1299 5788
409154 interferon-induced protein 35 U72882 Hs 50842 41 3143155028
438662 cleavage and polyadenylation specific f AA223599 Hs 6351 41 3345 7330 424800 MyoD family inhibitor AL035588 Hs 153203 41 200220036300
435408 ESTs, Weakly similar to T29299 hypothet H07897 Hs 4302 41 3125 7141
418526 solute earner family 16 (monocarboxyli BE019020 Hs 85838 41 1251 5752
402474 NM_004079 Homo sapiens cathepsm S (CTS 41
429599 ESTs AA806106 Hs 123664 41 2583 6724 438708 Homo sapiens phenylalkylam e binding p BE279778 Hs 30619 41 3352 7336
435575 triggering receptor expressed on myeloi AF213457 Hs 44234 4 1 313931407152
426363 transforming growth factor, beta 3 M58524 Hs 2025 41 22102211 6446
410036 calsequestππ 2 (cardiac muscle) R57171 Hs 57975 41 412 5100
407874 Homo sapιens cDNA FLJ14059fis, clone HAI766311 Hs 289047 41 175 4918 430255 Homo sapiens mRNA for KIAA1551 protein, AK000703 Hs 323822 41 266926706785
451149 RNA binding motif protein 8B AL047586 Hs 10283 41 4214 8073
425289 interferon, gamma inducible protein 16 AW139342 Hs 155530 41 2082 6358
424665 caveolm 2 AW368576 Hs 139851 41 1985 6288
434815 corel UDP-galactose -acetylgalactosamιAF155582 Hs 46744 41 307630777100 431448 hypothetical protein DKFZp56401278 AL137517 Hs 306201 41 278527866869
453149 DKFZP434G145 protein BE614781 Hs 31931 41 4395 8221
434203 hypothetical protein PR01855 BE262677 Hs 283558 41 3033 7066
432169 phosphoπbosyl pyrophosphate synthetase Y00971 Hs 2910 41 284728486914
418400 KIAA0246 protein BE243026 Hs 301989 41 1234 5739 418990 proteasome (prosome, macropain) subunit BE410285 Hs 89545 41 1289 5780
452281 Homo sapiens CDNA FLJ11041 fis, clone P T93500 Hs 28792 41 4309 8149
448603 DNA segment on chromosome X and Y (uniq L03426 Hs 21595 41 401740187911
432842 hypothetical protein MGC4485 AW674093 Hs 334822 41 2911 6966
431124 doublesex and mab-3 related transcript! AF284221 Hs 59506 41 275327546843 449609 guanine nucleotide binding protein (G p BE246434 Hs 289026 41 4099 7980
422085 zinc finger protein 294 AB018257 Hs 288773 41 163916406039
422532 protective protein for beta galactosida AL008726 Hs 118126 41 169716986083
424792 origin recognition complex, subunit 5 ( U92538 Hs 153138 41 20002001 6299
446948 peroxisomal long chain acyl coA thioest BE409053 Hs 299629 41 3883 7800 408331 dual specificity phosphatase 12 NMJ07240 Hs44229 41 211 2124948
417601 KIAA0215 gene product NMJ14735 Hs 82292 41 113611375664
449129 ESTs AI631602 Hs 258949 41 4066 7950
420890 6 phosphogluconolactonase AA434058 Hs 100071 41 1488 5931
431735 thymosin, beta 4, X chromosome AW977724 Hs 356629 41 2815 6890 452093 Homo sapiens mRNA, cDNA DKFZp586M0723 ( AA447453 Hs 27860 41 4286 8129
435937 ESTs AA830893 Hs 119769 41 3164 7172
450755 ESTs AA010984 Hs 159464 41 4190 8054
407214 CGI-39 protein, cell death-regulatory p AA412048 Hs 279574 41 122 4874
444367 hypothetical protein FLJ22390 H54892 Hs 10974 41 3695 7650 443351 Homo sapiens CDNA FLJ13471 fis, clone PAW016783 Hs 30799 41 3617 7583
434001 angiotensmogen AW950905 Hs 3697 41 3022 7055
446231 interferon consensus sequence binding p NM_002163 Hs 1 4453 41 382738287755
446618 COP9 subunit 6 (M0V34 homolog, 34 kD) AU 10307 Hs 15591 4 1 3860 7781
433800 lung type-l cell membrane-associated gl AI034361 Hs 135150 41 3004 7040 421379 small inducible cytokine subfamily B (C Y15221 Hs 103982 41 1535 15365967
419652 hypothetical protein AL157485 Hs 91973 41 1367 5840 420911 0 linked N acetylglucosamine (GlcNAc) t U77413 Hs 100293 41 149114925934 447198 ESTs D61523 Hs 283435 41 38987814 407239 leukocyte immunoglobulm-like receptor, AA076350 Hs 67846 41 1294879 412582 proteaso e (prosome, macropam) subunit BE270631 Hs 74077 41 6115254 444143 ESTs, Moderately similar to A56194 thro AW747996 Hs 160999 41 36797637 444914 WD repeat domain 13 AA046947 Hs 12142 40 37347680 446936 ESTs H10207 Hs 47314 40 38807798 449030 Homo sapiens mRNA for FLJ00016 protein, AI365582 Hs 57100 40 40597943 424806 MSTP031 protein AA382523 Hs 105689 40 20046301 423550 ESTs F37675 Hs 152129 40 18156169 437741 putative transmembrane protein, homolog BE561610 Hs 5809 40 32837276 430713 eukaryotic translation elongation facto AA351647 Hs 2642 40 27266824 439551 ESTs W72062 Hs 11112 40 34067389 409208 integrin, alpha X (antigen CD11 C (p150) Y00093 Hs 172631 40 3263275038 431468 nuclear prelam A recognition factor AW248431 Hs 256526 40 27906872 433364 ESTs, Moderately similar to I54374 gene A1075407 Hs 296083 40 29727013 435520 HNOEL-iso protein AA297990 Hs 9315 40 31307146 427897 apelin, peptide ligand for APJ receptor NM..017413 Hs 303084 40 238223836570 419431 actin related protein 2/3 complex, subu AW805152 Hs 90370 40 13375819 443727 ESTs Z25389 Hs 18459 40 36407603 420842 hypothetical protein MGC10986 AI083668 Hs 50601 40 14855929 451118 ESTs AI862096 Hs 60640 40 42138072 426530 complement component 4A U24578 Hs 278625 40 224922506472 451811 hypothetical protein MGC1136 AA663485 Hs 8719 40 42598106 456629 histone deacetylase 3 AW891965 Hs 367942 40 45268329 417374 ESTs D44865 Hs 86045 40 11065644 422675 eukaryotic translation initiation facto BE018517 Hs 381005 40 17256104 400295 AI905687 IL-BT095-190199 019 BT095 Homo W72838 Hs 348419 40 64617 447560 phospholipase A2, group IVC (cytosolic, AF065214 Hs 8858 40 393739387845 414831 protein kinase, cAMP-dependent, regulat M31158 Hs 77439 40 8788795466 448413 ESTs AI745379 Hs 42911 40 40037900 406782 gb zw20f11 s1 Soares ovary tumor NbHOT AA430373 40 654832 424006 CD84 antigen (leukocyte antigen) AF054815 Hs 137548 40 188518866219 427668 hypothetical protein FLJ14904 AA298760 Hs 180191 40 23576551 423201 growth hormone receptor NM_000163 Hs 1 25180 40 178217836146 413995 syntaxin 1A (brain) BE048146 Hs 75671 40 7615373 429614 hypothetical protein MGC4248 AI371172 Hs 211539 40 25886727 433545 ESTs AA868510 Hs 112496 40 29867025 426482 gb EST92649 Skin tumor I Homo sapiens c AA379768 40 22376464 422451 ESTs, Weakly similarto S65657 alpha 1C AA310753 Hs 72988 40 16846072 408106 Homo sapiens cDNA FU12417 fis, clone M AW152449 Hs 226469 40 1914933 417636 ESTs R08916 Hs 191212 40 11425668 436555 ESTs, Weakly similar to 2003319A ankyπ A1972007 Hs 304646 40 32007202 447164 vipinn, similar to inflammatory respo AF026941 Hs 17518 40 38947810 453046 ESTs, Highly similar to CA5B_HUMAN CARB AA284040 Hs 31535 39 43858212 438482 ESTs AA909229 Hs 371970 38 33277317 437390 ESTs A1125859 Hs 112607 37 32577253 421170 ESTs BE217797 Hs 126052 37 15135951 445492 ESTs AI240582 Hs 214678 36 37757712 459362 gb EST386176 MAGE resequences, MAGM Hom AW974073 36 45928388 405004 interleukin enhancer binding factor 1 36 4768 446028 Homo sapiens cDNA FLJ13136 fis, clone N R44714 Hs 106795 36 38127741 435039 ESTs AW043921 Hs 30526 36 30997118 458474 ESTs AW207346 Hs 143202 35 45758372 457976 ESTs A1222422 Hs 121846 34 45648361 421060 ESTs AA810953 Hs 89104 34 15025941 420147 ESTs AI918692 Hs 88109 32 14215882 437571 ESTs AA760894 Hs 125350 31 32717265 459034 ESTs BE550133 Hs 277254 30 45898385 408660 ESTs, Moderately similar to PC4259 ferr AA525775 Hs 89040 30 2474977 436202 ESTs AA706315 Hs 374191 26 31767181
TABLE 4B Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Numbi
439092 919640 J AW978407 AA830149 M85983 AW503637 BF352096
414315 203914 2 AA494098 Z24878 F13654 AA494040
418059 1164438 1 AA211586 F35799 F29720 AW937408 AW937387 AA211641
406636 0_0 L12064 L12083 L12065 L12075 L12066 L12085 L12072 L12082 L12081 L12062 L12080
411962 2307710 1 AA099050 AA099526 T47733
426413 372468 1 AW954494 AA377823 BG219617 BG195685 BG616269 AI022688
457567 1028609 1 AW970057 AW939073 AW940012 AW939074 AW939938 AW939206 AW939076 AA574383 BE160476 AA573577 AW750479
428048 140288 1 AA420433 AA420850 AA705745
430683 32178 -1 NA
40S782 0_0 AA430373 AA968771
426482 1296615 1 AA379768 AA379769 AA379568
459362 1238130 1 AW974073 T56957
TABLE 4C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers Dunham I et al refers to the publication entitled "The DNA sequence of human chromosome 22 " Dunham l et al , Nature (1999) 402489 495
Strand Indica tes DNA strand from wh nch exons were predicted
NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
405001 6015406 Minus 104646-104819
403593 6862650 Minus 62554-62712,69449-69602
403088 8954241 Plus 169894-170193,170504-170806
400499 9796071 Minus 148495-148806
401403 7710966 Plus 146180-146294
403081 8954241 Plus 155749-156048,156142-156459
401566 8469090 Minus 96277-96420,96979-97160
403087 8954241 Plus 169511-169795
402507 9797889 Plus 118979-119086
403071 8954241 Plus 136688-137096
406387 9256180 Plus 116229-116371,117512-117651
403362 8571772 Plus 64099 64260
401961 4581193 Minus 124054-124209
403086 8954241 Plus 169170-169412
402621 9930950 Plus 130806-131036
402408 9796239 Minus 110326-110491
405259 7329310 Plus 137102-137224,137698-137821
404977 3738341 Minus 43081-43229
400528 6981824 Plus 472381-472528,474170-474277,475328-47554
402855 9662953 Minus 59763 59909
403074 8954241 Plus 143375-143561
403291 7230870 Plus 95177-95435
402685 8318556 Plus 58962-59294
400517 9796686 Minus 49996 50346
400991 8096825 Plus 159197-159320
406519 3962489 Plus 34617-34928
402474 7547175 Minus 53526-53628,55755-55920,57530-57757
405004 6015406 Minus 186054-186365
TABLE 5A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of synovial sarcoma AIs divided by the 50* percentile of normal tissue AIs, where the 10th percentile of normal tissue
AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
420208 silver (mouse homolog) like BE276055 Hs 95972 25 1 1431 5891
451497 Wnt inhibitory factor-1 H83294 Hs 284122 17 5 4235 8089
452838 preferentially expressed antigen in mel U65011 Hs 30743 165 435743588188
441134 cellular retmoic acid-binding protein W29092 Hs 346950 16 3 3500 7475
445160 sine oculis homeobox (Drosophila) homol AI299144 Hs 101937 16 1 3748 7692
422424 prostate differentiation factor AI186431 Hs 296638 148 1681 6070
419628 ESTs H67546 Hs 49768 148 1364 5837
424687 matrix metalloproteinase 9 (gelatmase J05070 Hs 151738 14 1 1986 19876289
436485 immunoglobulin kappa constant X59135 Hs 156110 129 319331947198
452223 hypothetical protein MGC2827 AA425467 Hs 8035 126 4302 8142
417153 collagen, type II, alpha 1 (pnmary ost X57010 Hs 81343 125 1084 10855625
413916 apolipoprotein C-ll N49813 Hs 75615 123 753 5367
413063 chitinase 3-lιke 1 (cartilage glycoprot AL035737 Hs 75184 123 676 5308
418678 cancer/testis antigen (NY-ESO-1) NMJ01327 Hs 8 225 122 1269 12705765
442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 12 1 3551 7523
426600 VGF nerve growth factor inducible NM_003378 Hs 1 71014 11 9 225522566475
419556 chitinase 1 (chitotnosidase) U29615 Hs 91093 11 9 1351 13525829
414812 monokine induced by gamma interferon X72755 Hs 77367 11 6 8748755464
447377 transcription factor AP-2 alpha X77343 Hs 334334 11 0 39203921 7831
430377 dopachrome tautomerase (dopachrome delt M_001922 Hs 301865 103 268226836795
446921 small inducible cytokine subfamily A (C AB012113 Hs 16530 103 387838797797
431958 cadhenn 3, type 1, P-cadheπn (placent X63629 Hs 2877 10 2 283428356904
404854 Target Exon 10 1 4762
426555 tyrosiπase (oculocutaneous albinism IA) NM 000372 Hs 2053 100 2251 22526473
428398 ESTs AI249368 Hs 98558 100 2435 6614
429083 BCL2-related protein A1 Y09397 Hs 227817 99 25102511 6670
450149 Zic family member 2 (odd paired Drosoph AW969781 Hs 132863 98 4136 8011
453837 baculoviral IAP repeat containing 7 (Ii AL138387 Hs 256126 97 4448 8265
406663 immunoglobulin heavy constant mu U24683 97 39404818
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 96 1669 16706062
450390 Human DNA sequence from clone RP11-234G 93227 Hs 348805 95 4163 8031
426300 delta like homolog (Drosophila) U15979 Hs 169228 94 2196 21976437
428289 complement component 2 M26301 Hs 2253 93 2421 2422 6603
458079 Homo sapiens similar to RIKEN cDNA 2810 AI796870 Hs 381220 92 4566 8363
433447 πeuronal pentraxin II U29195 Hs 3281 9 1 29802981 7021
431830 small inducible cytokine subfamily A (C Y16645 Hs 271387 90 282728286900
408380 diubiquitm AF123050 Hs 44532 90 2172184952
403349 ephπn-B3 90 4714
412719 ESTs AW016610 Hs 816 89 633 5270
432874 melanoma inhibitory activity W94322 Hs 279651 8 9 2913 6968 427527 immunoglobulin heavy constant mu AI809057 Hs 153261 89 2340 6536
427634 hypothetical protein MGC10820 AI399745 Hs 18449 88 2352 6546
451668 cartilage acidic protein 1 Z43948 Hs 326444 88 4242 8094
412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 88 569 5220
418054 lysyl oxidase-like 2 NMJ02318 Hs 83354 88 118411855702
424001 paternally expressed 10 W67883 Hs 137476 87 1882 6217
430822 gIyceraldehyde-3-phosphate dehydrogenas AJ005371 Hs 248017 87 2729 27306827
419833 Homo sapiens tryptophanyl-tRNA syntheta AA251131 Hs 220697 87 1388 5856
447499 protocadhenn beta 16 AW262580 Hs 147674 86 3934 7842
418506 Unknown protein for MGC 29643 (formerly AA084248 Hs 372651 86 1247 5748
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 85 3057 7083
417308 KIAA0101 gene product H60720 Hs 81892 84 1094 5634
447210 phosphatidylsenne-specific phospholipa AF035269 Hs 17752 84 390239037818
416640 neuron-specific protein BE262478 Hs 13406 84 1019 5576
407233 carcinoembryonic antigen-related cell a X16354 Hs 50964 83 126 1274877
417389 midkine (neuπte growth-promoting facto BE260964 Hs 82045 83 1109 5647
408915 heptacellular carcinoma novel gene-3 pr NM 016651 Hs 48950 82 2742754998
409361 sine oculis homeobox (Drosophila) homol NM 005982 Hs 54416 82 3443455049
437898 ESTs W81260 Hs 43410 80 3293 7286
406837 immunoglobulin kappa constant R70292 Hs 156110 79 69 4836
418867 msh (Drosophila) homeo box homolog 2 D31771 Hs 89404 79 1277 12785772
406672 major histocompatibility complex, class M26041 Hs 198253 79 43444820
441633 normal mucosa of esophagus specific 1 AW958544 Hs 112242 78 3529 7501
428227 small inducible cytokine subfamily B (C AA321649 Hs 2248 77 2410 6593
424170 hypothetical protein MGC2827 AA337449 Hs 8035 77 1908 6236
421563 granulysin NM 006433 Hs 1 05806 77 1561 15625983
421592 bagpipe homeobox (Drosophila) homolog 1 AF009801 Hs 105941 77 1569 15705988
438915 Williams-Beuren syndrome chromosome reg AA2801 4 Hs 355711 76 3365 7348
424800 MyoD family inhibitor AL035588 Hs 153203 76 200220036300
409103 XAGE-1 protein AF251237 Hs 112208 76 3043055021
402992 Target Exon 76 4700
406684 carcinoembryonic antigen-related cell a X16354 Hs 50964 76 126 1274822
418064 S100 calcium-binding protein, beta (neu BE387287 Hs 83384 76 1188 5705
442711 hypothetical protein AF151073 Hs 8645 75 357935807549
410361 guaπylate binding protein 1, interferon BE391804 Hs 62661 75 456 5132
440042 ESTs AI073387 Hs 133898 74 3448 7430
418140 microfibπllar-associated protein 2 BE613836 Hs 83551 74 1196 5713
411027 leukocyte immunoglobulin-like receptor, AF072099 Hs 67846 73 5095105170
446619 secreted phosphoprotein 1 (osteopontm, AU076643 Hs 313 73 3861 7782
434175 ESTs AW979081 Hs 165469 73 3032 7065
431779 apolipoprotein C-l AW971178 Hs 268571 73 2820 6894
452203 transporter 1, ATP-bindmg cassette, su X57522 Hs 352018 73 429842998140
419741 ubiquitin carrier protein E2-C NM_007019 Hs 93002 73 1379 13805850
406698 major histocompatibility complex, class X03068 Hs 73931 72 51 524824
417355 eπdothelin receptor type B D13168 Hs 82002 72 1100 1101 5640
448357 RAB38, member RAS oncogene family N20169 Hs 108923 72 3994 7893
417437 interferon regulatory factor 4 U52682 Hs 82132 72 1123 11245656
427558 growth differentiation factor 10 D49493 Hs 2171 72 234523466540
420267 ESTs N37030 Hs 173337 72 1441 5898
432247 ESTs AA531287 Hs 105805 72 2859 6923
432800 AIM-1 protein BE391046 Hs 278962 71 2909 6964
452862 ADAMTS2 (a disintegπn-like and metall AW378065 Hs 8687 71 4360 8190
414312 ESTs AA155694 Hs 191060 70 800 5407
421815 membrane protein CH1 AW592146 Hs 108636 70 1598 6009
448140 BCM-like membrane protein precursor AF146761 Hs 20450 70 39803981 7882
409327 collagen, type IX, alpha 3 L41162 Hs 53563 70 341 3425047
427961 ESTs AW293165 Hs 143134 69 2388 6575
415989 ESTs AI267700 Hs 351201 69 962 5530
415052 mesenchyme homeo box 2 (growth arrest-s NM 005924 Hs 77858 69 9049055485
443184 ESTs A1638728 Hs 135159 68 3607 7574
414299 ESTs AA142989 Hs 71730 68 799 5406
424326 ADAM-like disintegnn protease, decysin NM_014479 Hs 1 45296 67 193419356252
409007 Homo sapiens mRNA, cDNA DKFZp434G0827 ( AL122107 Hs 49599 67 292 5012
410889 twist (Drosophila) homolog (acrocephalo X91662 Hs 66744 67 501 5025164
447674 cyclm-dependent kinase 2 BE270640 Hs 19192 66 3947 7854
406367 NM_022357 Homo sapiens putative metallo 66 4804
438568 major histocompatibility complex, class R98865 Hs 11135 66 3336 7324
421458 carbohydrate (keratan sulfate Gal-6) su NM 003654 Hs 1 04576 66 1543 15445972
414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 66 8768775465
407792 putative secreted ligand homologous to AI077715 Hs 39384 66 162 4906
420602 regulator of G-protein signalling 20 AF060877 Hs 99236 65 1469 14705918
404378 C7000450* gι|7768636|dbj|BAA95483 1| (A 65 4746
426991 Homo sapiens cDNA FLJ10674 fis, clone N AK001536 Hs 214410 65 2294 6502
449969 Homo sapiens cDNA FLJ14337 fis, clone P AW295142 Hs 180187 65 4123 8001
418203 CDC28 protein kinase 2 X54942 Hs 83758 65 1202 12035719
432098 cytochrome P450 retinoid metabolizing p AF252297 Hs 91546 65 2839 28406908
429986 sine oculis homeobox (Drosophila) homol AF092047 Hs 227277 65 263226336759
453883 cofactor required for Sp1 transcription AI638516 Hs 347524 65 4459 8273
401797 Target Exon 65 4663
445337 fibronectin leucine rich transmembrane NM_013280 Hs 1 2523 65 37603761 7701
408212 hypothetical protein AA297567 Hs 43728 65 206 4945
406868 immunoglobulin heavy constant gamma 3 ( AA505445 Hs 300697 65 72 4839
421379 small inducible cytokine subfamily B (C Y15221 Hs 103982 64 1535 15365967
417370 tryptophanyl-tRNA synthetase T28651 Hs 374466 64 1105 5643
417166 Paired box protein Pax-3 AA431323 Hs 42146 64 1088 5628
403404 Target Exon 64 4718 433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 64 292329246977 412140 RAB6 interacting, kinesm-like (rabkine AA219691 Hs 73625 64 573 5223 423673 matrix metalloproteinase 12 (macrophage BE003054 Hs 1695 63 1837 6186 421241 transketolase like 1 X91817 Hs 102866 63 1519 15205956 447217 nβuropilin 2 BE465754 Hs 17778 63 3904 7819 425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 63 209921006369 436557 ESTs, Weakly similar to A47582 B-cell g W15573 Hs 271272 63 3201 7203 449294 ESTs AI651786 Hs 195045 63 4079 7961 448961 ESTs AI610643 Hs 187285 63 4052 7937 423739 ESTs AA398155 Hs 97600 63 1842 6190 416208 ESTs, Weakly similar to MUC2_HUMAN MUCI AW291168 Hs 41295 6 3 981 5548 431290 cadheπn-like 22 AF035300 Hs 264157 6 2 2771 27726857 433075 sortilin 1 NM_002959 Hs 351872 62 293629376987 406621 immunoglobulin lambda locus X57809 Hs 181125 6 1 26274810 438549 tπnucleotide repeat containing 3 BE386801 Hs 21858 6 1 3331 7320 448390 hypothetical protein AL035414 Hs 21068 61 3999 7897 428865 BarH-like homeobox 1 BE544095 Hs 164960 6 1 2485 6651 424408 collagen, type V, alpha 1 AI754813 Hs 146428 6 1 1943 6260 413385 indoleamine pyrrole 2,3 dioxygenase M34455 Hs 840 6 1 710711 5331 404815 ENSP00000251989* DJ100N22 1 (NOVEL EGF- 60 4761 400295 AI905687 IL-BT095 190199 019 BT095 Homo W72838 Hs 348419 60 6 4617 442432 hypothetical protein FLJ23468 BE093589 Hs 38178 60 3563 7535 443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 6 0 3621 36227586 436481 HSPC150 protein similar to ubiquitin-co AA379597 Hs 5199 60 3192 7197 422846 neutrophil cytosolic factor 1 (47kD, ch BE513934 Hs 1583 60 1749 6120 436396 wingless type MMTV integration site fam A1683487 Hs 152213 60 3184 7189 444381 hypothetical protein BC014245 BE387335 Hs 283713 59 3697 7652 404030 NM_015669* Homo sapiens protocadhenn b 59 4735 434916 Homo sapiens, Similar to RIKEN cDNA 111 AF161383 Hs 284207 5 9 3091 30927111 402888 Target Exon 5 9 4698 453271 ESTs AA903424 Hs 6786 59 44098232 409637 Homo sapiens mRNA, cDNA DKFZp434K0621 (AA323948 Hs 55407 58 3725069 403857 Target Exon 58 4730 422910 Human DNA sequence from PAC 257A7 on ch AI269508 Hs 191979 58 17586127 441544 ESTs AW300043 Hs 127137 5 8 35237496 415323 neutrophil cytosolic factor 2 (65kD, ch BE269352 Hs 949 5 8 9235499 409415 Homo sapiens cDNA FLJ21028 fis, clone AA579258 Hs 6083 58 3475051 433068 sialyltransferase NM 006456 Hs 288215 58 293429356986 430643 MEGF10 protein AW970065 Hs 287425 58 27176817 407826 calpam 3, (p94) AA128423 Hs 40300 5 8 1674911 441859 interleukin 4 induced gene-1 protein (F AW194364 Hs 380444 5 8 35407512 447414 neuroblastoma (nerve tissue) protein D82343 Hs 74376 58 392439257834 457869 Homo sapiens, alpha 1 (VI) collagen AU077186 Hs 108885 58 45618359 451766 ephnn B3 NMJ01406 Hs 26988 58 425542568104 448719 tnnucleotide repeat containing 3 AA033627 Hs 21858 5 8 40287920 413794 myosin X AF234532 Hs 61638 57 7417425357 452620 ESTs AA436504 Hs 119286 57 43388172 411252 MD-2 protein AB018549 Hs 69328 57 5215225181 427528 minichromosome maintenance deficient (S AU077143 Hs 179565 57 23416537 423013 secreted modular calcium-binding protei AW875443 Hs 22209 57 17696135 446291 interferon, gamma- ducible protein 30 BE397753 Hs 14623 57 38337760 425234 ESTs, Weakly similarto I38022 hypothet AW152225 Hs 165909 56 20706349 420028 carbohydrate (N-acetylglucosamιne-6 O) AB014680 Hs 8786 56 140814095872 405542 Target Exon 56 4789 453173 KIAA0442 protein AB007902 Hs 32168 5 6 439743988223 437044 differentially expressed in Fanconi's a AL035864 Hs 69517 56 32337232 428484 solute earner family 7 (cationic ammo AF104032 Hs 184601 56 244924506624 440650 Human DNA sequence from PAC 75N13 on ch R44692 Hs 326801 56 34777455 449722 cyclin B1 BE280074 Hs 23960 56 41127990 435124 ESTs AA725362 Hs 75514 56 31077125 429359 matrix metalloproteinase 14 (membrane-i W00482 Hs 2399 56 25516702 421633 sorting πexin 10 AF121860 Hs 106260 56 157215735990 426514 bone morphogenetic protein 7 (osteogeni BE616633 Hs 170195 56 22466470 436608 down syndrome critical region protein D AA628980 Hs 192371 56 32057207 418110 hypothetical protein FLJ22202 R43523 Hs 217754 56 11935710 427923 FGENESH predicted 11 TM protein AW274357 Hs 301406 56 23856572 429903 cyclm-dependent kinase 5, regulatory s AL134197 Hs 93597 56 26166746 451763 hypothetical protein FLJ14220 AW294647 Hs 233634 56 42548103 408209 ets variant gene 5 (ets-related molecul NM_004454 Hs 43697 56 2042054944 443378 proteasome (prosome, macropaiπ) subunit AW392550 Hs 381081 56 36187584 452194 olfactory receptor, family 2, subfamily AI694413 Hs 373599 5 6 42958137 452363 Homo sapiens, Similar to complement com AI582743 Hs 94953 56 43228159 438746 Human melanoma associated antigen p97 ( AI885815 Hs 184727 55 33537337 429170 dual specificity phosphatase 4 NMJ01394 Hs 2 359 55 252425256680 419236 Homo sapiens cDNA FLJ11481 fis, clone H AA330447 Hs 135159 55 13215805 452319 transduαn-like enhancer of split 1, ho M99435 Hs 28935 55 431343148152 406782 gb zw20f11 s1 Soares ovary tumor NbHOT AA430373 55 654832 430439 DKFZP434B061 protein AL133561 Hs 380155 5 5 269526966803 453392 SRY (sex determining region Y) box 11 U23752 Hs 32964 55 441644178239 420842 hypothetical protein MGC10986 AI083668 Hs 50601 55 14855929 413367 solute carπerfamily 16 (monocarboxyli NM_006517 Hs 7 5317 55 7067075329 448985 carbonic anhydrase XI AA324885 Hs 22777 55 40547939 412939 eukaryotic translation elongation facto AW411491 Hs 75069 55 6575292 400229 NMJ21724* Homo sapiens nuclear recepto Hs 276916 55 4602 452281 Homo sapιens cDNA FLJ11041 fis, clone P T93500 Hs 28792 5 5 43098149 412471 endothelial cell growth factor 1 (plate M63193 Hs 73946 55 5915925239 406836 immunoglobulin kappa constant AW514501 Hs 156110 55 68 4835
404240 NM 018950 Homo sapiens major histocompa 54 4742
428949 hypothetical protein DKFZp434J0617 AA442153 Hs 104744 54 2490 6655
407846 Cbp/p300 interacting transactivator, wi AA426202 Hs 40403 54 169 4913
458208 ESTs, Weakly similar to T4S4.HUMAN TRAN AI380016 Hs 352394 54 4570 8367
423639 KIAA1405 protein AB037826 Hs 130411 54 1831 18326183
405451 Homo sapiens glutammyl-peptide cyclotr 54 4783
400263 Eos Control Hs 75309 54 4613
417007 chloride channel 7 AF224741 Hs 80768 54 1058 10595604
403402 Target Exon 53 4717
418956 KIAA0788 protein AA234831 Hs 348493 53 1287 5778
452698 chemokme (C-C motif) receptor 1 NMJ01295 Hs 301921 53 434343448177
424481 proteolipid protein 1 (Pelizaeus-Merzba R19453 Hs 1787 53 1960 6272
450056 ESTs, Weakly similar to S71512 hypothet BE047394 Hs 502 53 4129 8005
416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 53 1001 10025564
446142 ESTs AI754693 Hs 145968 53 3820 7748
402474 NMJ04079 Homo sapiens cathepsm S (CTS 53 4682
411089 cell division cycle 2-lιke 1 (PITSLRE p AA456454 Hs 214291 53 513 5173
406636 gb Homo sapiens (clone WR4 12VL) anti-t L12064 53 32334814
419749 sparc/osteonectm, cwcv and kazal like X73608 Hs 93029 52 1383 13845852
409430 splicing factor, arginine/seπne πch 5 R21945 Hs 346735 52 348 5052
416975 granzyme B (granzyme 2, cytotoxic T-lym NM_004131 Hs 1 051 52 1052 10535600
436771 ESTs AW975687 Hs 292979 52 3214 7215
413936 senne (orcysteme) proteinase inhibit AF113676 Hs 297681 52 7557565369
418883 acid phosphatase 5, tartrate resistant BE387036 Hs 1211 52 1281 5774
456974 apolipoprotein E M12529 Hs 169401 52 453645378338
410011 PFTAIRE protein kinase 1 AB020641 Hs 57856 52 4064075096
448075 ESTs, Weakly similar to alpha-1 type 2 AW583284 Hs 286747 52 3975 7877
443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 52 3656 7617
443021 lg superfamily protein AA368546 Hs 8904 52 3593 7561
407239 leukocyte immunoglobulin like receptor, AA076350 Hs 67846 51 129 4879
425262 GS3955 protein D87119 Hs 155418 51 207620776354
422836 AKAP-binding sperm protein roppoπn AL037365 Hs 194093 51 1748 6119
417728 KIAA1573 protein AW138437 Hs 24790 51 1151 5675
432485 CDW52 antigen (CAMPATH-1 antigen) \N90866 Hs 276770 51 2877 6939
424825 procollagen lysine, 2 oxoglutarate 5 di AF207069 Hs 153357 5 1 200520066302
443071 complement component 1, q subcomponent, AL08002' I Hs 8986 5 1 3598 7566
432693 ESTs AW449630 Hs 293790 51 2900 6958
414034 early development regulator 1 (homolog U89277 Hs 305985 51 771 7725381
409197 chromosome 11 open reading frame 24 N54706 Hs 303025 51 322 5035
446659 ESTs AI335361 Hs 226376 51 3865 7786
419870 phosphoprotein associated with GEMs AW403911 Hs 266175 5 1 1390 5858
433671 19A24 protein AW138797 Hs 132906 5 1 3000 7036
428862 SRY (sex determining region Y)-box 9 (c NM 000346 Hs 2316 51 2483 24846650
424378 neural cell adhesion molecule 1 W28020 Hs 167988 51 1940 6257
448569 signal transducer and activator of tran BE382657 Hs 21486 51 4014 7909
415752 putative transmembrane protein BE314524 Hs 78776 51 945 5517
420568 protocadhenn alpha 10 F09247 Hs 247735 51 1462 5913
407597 Homo sapiens brother of CDO (BOC) mRNA, AA043925 Hs 339352 50 143 4889
409893 minichromosome maintenance deficient (S AW247090 Hs 57101 50 397 5088
426418 collagen, type IV, alpha 5 (Alport synd M90464 Hs 169825 50 22202221 6454
438937 ESTs AW952654 Hs 73964 50 3367 7350
417796 ESTs AA206141 Hs 367818 50 1159 5682
400235 NM_005336 Homo sapiens high density lip Hs 177516 50 4604
436748 collagen, type VI, alpha 2 BE159107 Hs 159263 50 3212 7213
403668 Target Exon 50 4727
437330 Homo sapiens mRNA cDNA DKFZp761J1112 ( AL353944 Hs 50115 50 3253 7250
434431 ESTs AW131454 Hs 168571 50 3056 7082
453344 ESTs BE349075 Hs 44571 50 4415 8238
453139 Human DNA sequence from clone RP11-234G AA330620 Hs 3488055 0 4394 8220
431590 sema domain transmembrane domain (TM), AB037789 Hs 263395 50 28002801 6879
448595 KIAA0644 gene product AB014544 Hs 21572 50 401540167910
418299 integrin, beta 2 (antigen CD18 (p95), I AA279530 Hs 83968 50 1212 5725
411296 growth suppressor 1 BE207307 Hs 10114 49 524 5183
438564 major histocompatibility complex, class AA381553 Hs 198253 49 3335 7323
440274 scrapie responsive protein 1 R24595 Hs 7122 49 3464 7443
435461 ESTs A1075846 Hs 133996 49 3127 7143
424870 ESTs T15545 Hs 244624 49 2014 6308
421707 lectomedιn-2 NM 014921 Hs 1 07054 49 1581 15825995
436291 protein regulator of cytokinesis 1 BE568452 Hs 344037 49 3180 7185
444090 natural killer cell group 7 sequence S69115 Hs 10306 49 367536767634
424340 ESTs AA339036 Hs 7033 49 1937 6254
412659 olfactomedin related ER localized prate AW753865 Hs 74376 49 627 5265
414024 gb zm79g08 r1 Stratagene neuroepithe u AA134712 Hs 22410 49 769 5379
408161 hypothetical protein MGC3032 AW952912 Hs 300383 49 195 4937
452445 Homo sapiens mRNA from chromosome 5q21- AB002438 Hs 26339549 4332 8166
430265 stromal cell deπved factor 1 L36033 Hs 237356 49 2671 26726786
443254 ESTs AW450180 Hs 65788 49 3612 7579
446630 Homo sapiens mRNA, cDNA DKFZp434E033 (f AW384793 Hs 23960 48 3863 7784
409698 short stature homeobox 2 AF022654 Hs 55967 48 3783795074
414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 48 789 5397
435977 brain-specific membrane anchored protei AL138079 Hs 5012 48 3166 7174
414020 small inducible cytokine A4 (homologous NM 002984 Hs 75703 48 7677685378
427400 hypothetical protein FLJ11939 AW245084 Hs 94229 48 2325 6525
427019 hypothetical protein FLJ10970 AA001732 Hs 173233 48 2296 6504
439570 ESTs, Weakly similar to ALU1JHUMAN ALU T79925 Hs 269165 48 3407 7390 439979 hypothetical protein FLJ10430 AW600291 Hs 6823 3442 7424 412507 EphA4 L36645 Hs 73964 5965975243 414142 hemicentm (fibulin 6) AW368397 Hs 334485 781 5390 453857 Ras induced senescence 1 (RIS1) AL080235 Hs 35861 444944508266 442910 ESTs, Weakly similar to T19326 hypothet AI365130 Hs 11307 3589 7557 403405 Target Exon 4719 407241 gb Human omega light chain protein 14 1 M34516 1301314880 410342 Fc fragment of IgE, high affinity I, re R31350 Hs 743 4535129 435080 hypothetical protein FLJ14428 AI831760 Hs 155111 31037122 453237 ESTs AI969448 Hs 34578 4405822 424717 wingless-type MMTV integration site fam H03754 Hs 152213 19896291 413278 interferon stimulated protein, 15 kDa BE563085 Hs 833 6955322 404977 Insulin-like growth factor 2 (somatomed 4766 409208 integnn, alpha X (antigen CD11C (p150) Y00093 Hs 172631 3263275038 437862 Homo sapiens mRNA, cDNA DKFZp586C0224 (AW978107 Hs 5884 48 32917284 439737 Homo sapιens mRNAfull length ιnsertcD AI751438 Hs 41271 48 34277410 447343 ESTs, Highly similar to S02392 alpha 2- AA256641 Hs 236894 48 39167828 422799 neurexophilin 4 AI933199 Hs 120911 48 17386113 416350 phospholipase A2, group IID AF188625 Hs 189507 48 9939945557 429150 smoothened (Drosophila) homolog AF120103 Hs 197366 48 251925206677 454390 KIAA0906 protein AB020713 Hs 56966 48 449744988304 416135 ESTs AW473656 Hs 227277 47 9765543 432878 Piπn BE386490 Hs 279663 47 29146969 423232 leuciπe-πch neuronal protein BE244625 Hs 125742 47 17876149 453914 fructose-1,6-bιsphosphatase 1 NM-.000507 Hs 574 47 446544668278 421779 wingless type MMTV integration site fam AI879159 Hs 108219 47 15926004 418558 Fas (TNFRSF6)-assocιated via death doma AW082266 Hs 86131 47 12555755 418322 cyclin dependent kinase inhibitor 3 (CD AA284166 Hs 84113 47 12145727 446051 ephnn A3 BE048061 Hs 37054 47 38167744 422616 seleπophosphate synthetase 2 BE300330 Hs 118725 47 17136095 448886 hypothetical protein FLJ10357 AL137291 Hs 22451 47 404740487934 425934 Homo sapiens clone 25187 and 25188 mRNA AF131842 Hs 163642 47 215521566407 452683 progesterone membrane binding protein A1089575 Hs 374574 47 43418175 429612 pituitary tumor-transforming 1 AF062649 Hs 252587 47 258625876726 437723 ESTs AI672731 Hs 13256 47 32827275 453083 contactm associated protein 1 U87223 Hs 31622 47 438843898215 418323 major histocompatibility complex, class NM..002118 Hs 1 162 47 121512165728 419113 ESTs AI446586 Hs 21835 47 13055793 416801 sal (Drosophila) like 2 X98834 Hs 79971 47 10325585 426076 gb EST374787 MAGE resequences, MAGG Hom AW962714 47 21716418 412773 similar to vaccinia virus Hindlli K4L O H15785 Hs 74573 47 6395276 455813 gb QV2-HT0083 071299-018-a11 HT0083 Hom BE141577 47 45098315 427658 nogo receptor H61387 Hs 30868 47 23556549 427337 Fc fragment of IgG, low affinity lllb, Z46223 Hs 176663 47 231823196521 412609 ocular albinism 1 (Nettleship-Falls) Z48804 Hs 74124 47 6156165257 449523 chemokme (C-C motif) receptor 5 NM..000579 Hs 54443 47 409440957976 456508 ESTs, Weakly similar to AF208855 1 BM-0 AA502764 Hs 123469 47 4521 8325 415019 nuclear factor of activated T-cells, cy AI674651 Hs 77810 47 9015482 428839 Homo sapiens cDNA FLJ14814 fis, clone N AI767756 Hs 82302 46 24806648 432383 Homo sapiens cDNA FLJ20137 fis, clone C AK000144 Hs 274449 46 28686931 437879 hypothetical protein FLJ10305 BE262082 Hs 5894 46 32927285 434276 leucine zipper, putative tumor suppress AF123659 Hs 93605 46 303930407070 444410 ESTs, Moderately similar to S65657 alph BE387360 Hs 33719 46 36997654 426470 ESTs AA528794 Hs 128644 46 22326461 422481 DNAX-activation protein 10 AL050163 Hs 117339 46 168716886075 411789 Adlican AF245505 Hs 72157 46 5535545207 408561 hypothetical protein MGC13016 AI308037 Hs 84120 46 2394970 426150 BarH-like homeobox 2 NM_003658 Hs 1 67218 46 218021816425 450447 hypothetical protein P15 2 AF212223 Hs 25010 46 416841698036 414747 centromere protein F (350/400kD, mitosi U30872 Hs 77204 46 8618625455 400262 Eos Control Hs 75309 46 4612 422175 ESTs, Highly similar to T00391 hypothet N79885 Hs 6382 46 16576053 422397 MYEOV Myeloma overexpressed gene (in a AJ223366 Hs 116051 46 167816796068 423897 DKFZP434N178 protein AB033062 Hs 134970 46 186318646205 440952 ESTs AI291804 Hs 118101 46 34907466 449129 ESTs AI631602 Hs 258949 46 40667950 458098 metallothioπem 1E (functional) BE550224 Hs 351851 46 45678364 414359 cadheπn 11, type 2, OB cadhenn (osteo M62194 Hs 75929 46 8085413 439589 ESTs AF086409 Hs 379390 45 34097392 439219 ESTs N33883 Hs 41322 45 33827365 457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs 32399 45 45438344 410290 hypothetical protein DKFZp564A176 AA402307 Hs 322844 45 4495126 447208 hypothetical protein MGC5627 BE315291 Hs 237971 45 39017817 414175 hypothetical protein DKFZp761 D112 AI308876 Hs 103849 45 7865394 429918 ESTs AW873986 Hs 119383 45 26196748 414875 major histocompatibility complex, class H42679 Hs 77522 45 8835469 404277 NM_019111* Homo sapiens major histocomp 45 4744 424125 inhibm, beta B (activin AB beta polype M31669 Hs 1735 45 190019016230 400543 C10001466 gι|7299451|gb|AAF54640 1| (AE 45 4632 424247 lysozyme (renal amyloidosis) X14008 Hs 234734 45 192219236244 407049 NMJ21724* Homo sapiens nuclear recepto X72632 45 991004854 405104 Target Exon 45 4771 452242 gycosyltraπsferase R50956 Hs 159993 45 43058145 433867 hippocalcm-Iike 1 AK000596 Hs 3618 45 30117046 422363 replication factor C (activator 1) 3 (3 T55979 Hs 115474 45 16736065 448386 KIAA1329 protein AB037750 Hs 21061 45 399739987896 452466 hypothetical protein DKFZp564B052 N84635 Hs 29664 45 4334 8168
404721 NM_005596* Homo sapiens nuclear factor 45 4759
417079 interleukin 1 receptor antagonist U65590 Hs 81134 45 1073 10745616
401357 tumor protein D52 like 1 45 4650
426935 collagen, type I, alpha 1 NM_000088 Hs 172928 45 2288 22896498
415701 gamma glutamyl hydrolase (conjugase, fo NM_003878 Hs 78619 45 940941 5514
437681 Homo sapiens, Similar to TEA domain fam A1207958 Hs 166556 45 3280 7273
449444 solute carrier family 16 (moπocarboxyli AW818436 Hs 351306 45 4088 7970
451678 DKFZP564D0764 protein AA374181 Hs 26799 45 4244 8096
406648 major histocompatibility complex, class AA563730 Hs 277477 45 38 4817
450785 Homo sapiens, alpha 1 (VI) collagen AA852713 Hs 108885 45 4193 8056
402994 NMJ02463* Homo sapiens myxovirus (infl 45 4701
446962 muscle specific ring finger protein 1 AI351421 Hs 279709 45 3884 7801
416847 enhancer of filamentation 1 (cas like d L43821 Hs 80261 45 1039 10405590
435013 NM_020142 Homo sapiens NADH ubiquinone H9192 I Hs 110024 45 3096 7115
405770 NM J02362 Homo sapiens melanoma antigen 44 4796
400397 transcription factor 7-lιke 2 (T cell s AJ270770 44 18 194624
420591 neurotrophin 3 X53655 Hs 99171 44 1465 14665916
422007 ESTs AI739435 Hs 39168 44 1624 6029
429962 glutathione S transferase pi M69113 Hs 226795 44 2626 6754
438866 tissue inhibitor of metalloproteinase 2 U44385 Hs 6441 44 33603361 7344
439453 thyroid hormone receptor mteractor 13 BE264974 Hs 6566 44 3399 7382
408784 ESTs AW971350 Hs 63386 44 257 4986
444863 senne (or cysteme) proteinase inhibit AW384082 Hs 104879 44 3731 7677
400228 NM_021724* Homo sapiens nuclear recepto Hs 276916 44 4601
439318 G protein coupled receptor 56 AW837046 Hs 6527 44 3391 7374
422034 Ets2 repressor factor AC006486 Hs 333069 44 1627 1628 6032
419081 ESTs AI798863 Hs 87191 44 1299 5788
414883 CDC28 protein kinase 1 AA926960 Hs 348669 44 885 5471
450224 collagen type IV, alpha 6 D21337 Hs 408 44 41454146 8017
425308 receptor tyrosine kmase-like orphan re M97639 Hs 155585 44 208720886362
443801 iπtron of tnchorhmophalangeal syndr AW206942 Hs 253594 44 3646 7608
408787 Rho guanine exchange factor (GEF) 11 NM_014784 Hs 47822 44 258 2594987
424735 short chain alcohol dehydrogenase famil U31875 Hs 272499 44 1993 19946294
438596 ESTs AA829427 Hs 243081 44 3337 7325
435663 ESTs AI023707 Hs 134273 44 3143 7155
418990 proteasome (prosome macropain) subunit BE410285 Hs 89545 44 1289 5780
411365 GM2 ganglioside activator protein M76477 Hs 289082 44 5285295187
426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 44 2219 6453
400205 NMJ06265* Homo sapiens RAD21 (S pombe Hs 81848 44 4598
435176 ESTs AA744875 Hs 189413 44 3111 7129
448499 p53 regulated DDA3 BE613280 Hs 77550 44 4008 7905
443639 proteasome (prosome macropain) subunit BE269042 Hs 9661 44 3632 7595
418522 Homo sapiens cDNA FLJ21950 fis, clone AA605038 Hs 7149 44 1250 5751
421143 immunoglobulin superfamily containing I AB024536 Hs 102171 44 1510 1511 5949
430413 small inducible cytokine A5 (RANTES) AW842182 Hs 241392 44 2693 6801
418216 AF15q14 protein AA662240 Hs 283099 44 1206 5721
446751 Human DNAsequence from clone RP11-16L2 AA766998 Hs 378780 44 3871 7791
442328 ESTs, Weakly similar to ALU4.HUMAN ALU AI952430 Hs 150614 44 3556 7528
406973 major histocompatibility complex, class M34996 Hs 198253 43 9091 4849
418526 solute earner family 16 (moπocarboxyli BE019020 Hs 85838 43 1251 5752
426890 ESTs AA393167 Hs 41294 43 2283 6494
417142 ESTs AI082507 Hs 85905 43 1083 5624
429716 collagen type XIII, alpha 1 R25685 Hs 211933 43 2609 6741
427378 melanoma antigen, family D, 1 BE515037 Hs 177556 43 2322 6523
431639 phosphoprotein associated with GEMs AK000680 Hs 266175 43 28052806 6883
447198 ESTs D61523 Hs 283435 43 3898 7814
448258 hypothetical protein FLJ20396 BE386983 Hs 343214 43 3990 7889
407047 gb H sapiens SOD-2 gene for manganese s X65965 43 98 4853
439246 membrane associated tyrosine- and threo AI498072 Hs 351474 43 3386 7369
439709 hypothetical protein FLJ20128 AW401433 Hs 6649 43 3422 7405
404920 Target Exon 43 4765
405372 NMJ06841 Homo sapiens transporter prot 43 4778
412577 CD163 antigen Z22968 Hs 74076 43 6086095252
426283 kynurenmase (L-kynureniπe hydrolase) NM_003937 Hs 1 69139 43 219221936435
444371 forkhead box M1 BE540274 Hs 239 43 3696 7651
426759 ESTs AI590401 Hs 21213 43 2268 6483
436045 DKFZP564O0423 protein AB037723 Hs 5028 43 316931707176
433658 immunoglobulin kappa constant L03678 Hs 156110 43 2996 29977034
402876 NM J22161* Homo sapiens livin inhibitor 43 4697
409062 Homo sapiens mRNA cDNA DKFZp564B182 (fALI 57488 Hs 5015C I 43 301 5018
406642 gb Homo sapiens mRNA for immunoglobulin AJ24521C I 43 34354815
423989 OLF-1/EBF associated zinc finger gene AF221712 Hs 137168 43 1880 1881 6216
442547 ESTs Weakly similar to ALU1..HUMAN ALU AA306997 Hs 217484 43 3566 7537
422530 bone marrow stramal cell antigen 2 AW972300 Hs 118110 43 1696 6082
400802 Target Exon 43 4638
439627 hypothetical protein FLJ21841 BE621702 Hs 29076 43 3411 7394
418618 GTP cyclohydrolase 1 (dopa responsive d U66097 Hs 86724 43 1261 12625760
444119 ESTs, Weakly similar to T26686 hypothet R41231 Hs 184261 43 3677 7635
453910 Kruppel like zinc finger protein GLIS2 AL133794 Hs 16313 43 4464 8277
447737 DKFZP564L0862 protein AK000643 Hs 19404 43 395739587861
414945 lymphocyte antigen 6 complex locus E BE076358 Hs 77667 43 894 5477
437233 Homo sapiens brother of CDO (BOC) mRNA D81448 Hs 339352 43 3249 7246
403130 NM..005400* Homo sapiens protein kinase 43 4708
428291 interferon stimulated gene (20kD) AA534009 Hs 183487 43 2423 6604
418283 cathepsin K (pycnodysostosis) S79895 Hs 83942 43 1210 1211 5724 449611 ESTs AI970394 Hs 197075 43 4100 7981
412014 ESTs, Weakly similar to A46010 X-lmked AI620650 Hs 43761 43 566 5218
439540 ESTs AW979189 Hs 283367 43 3405 7388
408096 dihydrofolate reductase BE250162 Hs 83765 43 189 4931
419073 Homo sapiens cDNA FLJ12797 fis, clone N AW372170 Hs 183918 42 1296 5786
419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 42 1381 13825851
406634 GDP dissociation inhibitor 1 AA386235 Hs 74576 42 31 4813
454429 hypothetical protein PP3501 BE273437 Hs 301406 42 4500 8306
407818 jumonji (mouse) homolog AL021938 Hs 40154 42 165 4909
400261 Eos Control Hs 1802 42 4611
453597 myo-inositol 1-phosphate synthase A1 BE281130 Hs 381118 42 4429 8249
430622 Homo sapiens, Similar to DNA segment, C BE616971 Hs 247478 42 2714 6815
453204 ESTs R10799 Hs 191990 42 4403 8227
412926 macrophage myπstoylated alanine-nch C AI879076 Hs 75061 42 655 5290
432388 v-ski avian sarcoma viral oncogene homo X15218 Hs 2969 42 286928706932
455169 gb QV0-CT0387-170200-121-h07 CT0387 Hom AW860908 42 4505 8311
424842 signal transducing adaptor molecule (SH AA034127 Hs 153487 42 2013 6307
438451 ESTs AI081972 Hs 220261 42 3323 7313
421774 Homo sapiens mRNA, cDNA DKFZp586C1619 ( AL050374 Hs 10816942 1589 6001
418918 CD2 antigen (p50), sheep red blood cell X07871 Hs 89476 42 1282 12835775
452301 ESTs BE041144 Hs 127699 42 4312 8151
453779 28kD interferon responsive protein N35187 Hs 43388 42 4441 8259
427239 ubiquitiπ carrier protein BE270447 Hs 356512 42 2311 6515
443572 cleavage and polyadenylation specific f AA025610 Hs 9605 42 3625 7589
413048 mannose receptor, C type 1 M93221 Hs 75182 42 6726735305
423767 F-box only protein 2 H18283 Hs 132753 42 1845 6192
420162 cyclin-dependent kinase 4 BE378432 Hs 95577 42 1422 5883
421506 thymidine kinase 1, soluble BE302796 Hs 105097 42 1550 5976
418312 Ral guanine nucleotide exchange factor AW972468 Hs 170307 42 1213 5726
403508 Target Exon 42 4723
432729 hypothetical protein FLJ20285 AK000292 Hs 130732 42 290229036960
414085 aldehyde dehydrogenase 1 family, member AA114016 Hs 75746 42 775 5384
418113 SRY (sex determining region Y)-box 4 AI272141 Hs 83484 42 1194 5711
452106 ESTs AI141031 Hs 21342 42 4289 8131
429922 H1 histone family, member 0 Z97630 Hs 226117 42 2621 26226750
457400 cathepsm Z AF032906 Hs 252549 42 454745488347
420255 membrane metallo endopeptidase (neutral NMJ07289 Hs 1298 42 1438 14395896
417080 small nuclear ribonucleoprotem polypep BE392846 Hs 1063 42 1075 5617
445472 Homo sapiens mRNA for KIAA0293 gene, pa AB006631 Hs 12784 42 377337747711
453060 hypothetical protein MGC15754 AW294092 Hs 21594 42 4386 8213
414586 lymphocyte cytosolic protein 1 (L-plast AA306160 Hs 381099 42 833 5434
434669 core histone macroH2A22 AF151534 Hs 92023 41 306830697093
434149 hypothetical protein MGC5469 Z43829 Hs 244624 41 3030 7063
445333 hypothetical protein FLJ12538 similar t BE537641 Hs 44278 41 3759 7700
401176 Target Exon 41 4646
416926 HT018 protein H03109 Hs 263395 41 1046 5596
408196 SRY (sex determining region Y)-box 22 AL034548 Hs 43627 41 199 2004940
430422 ESTs AI078115 Hs 54680 41 2694 6802
411020 macrophage receptor with collagenous st NMJ06770 Hs 67726 41 5065075168
452436 ESTs, Moderately similar to A46010 X-Ii BE077546 Hs 31447 41 4330 8164
443264 ESTs, Moderately similar to A47582 B-ce BE221477 Hs 132137 41 3615 7581
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 41 1162 5685
431863 spmdlin AA188185 Hs 289043 41 2829 6901
422032 polymerase (RNA) III (DNA directed) pol AA476966 Hs 110857 41 1625 6030
440028 ESTs, Weakly similar to T17227 hypothet AW473675 Hs 367649 41 3446 7428
407756 ubiquitm specific protease 18 AA116021 Hs 38260 41 159 4903
452833 KIAA0124 protein BE559681 Hs 30736 41 4355 8186
429345 hypothetical protein R11141 Hs 199695 41 2548 6700
423447 ESTs D31043 Hs 282596 41 1807 6163
426501 ESTs AW043782 Hs 293616 41 2242 6467
429415 procollageπ C-eπdopeptidase enhancer NM 002593 Hs 202097 41 255725586706
446531 ESTs AW301023 Hs 150854 41 3854 7775
439668 frizzled (Drosophila) homolog 8 AI091277 Hs 302634 41 3414 7397
440087 hypothetical protein FLJ22678 W28969 Hs 7718 41 3452 7433
425170 transcription factor CP2 AU077315 Hs 154970 41 2061 6342
414522 Immunoglobulin J chain AW518944 Hs 76325 41 827 5428
406625 stearoyl-CoA desaturase (delta-9 desatu Y13647 Hs 119597 41 28 294811
400259 NM_017432* Homo sapiens prostate tumor Hs 19555 41 4610
438209 aryl hydrocarbon receptor nuclear trans AL120659 Hs 6111 41 3309 7301
446570 ESTs AV659177 Hs 127160 41 3858 7779
400252 NM_004651* Homo sapiens ubiquitm speci Hs 171501 41 4609
442739 cytosolic acyl coenzyme A thioester hyd NM 007274 Hs 8679 41 3581 35827550
419488 πucleophosmiπ/nucleoplasmin 3 AA316241 Hs 90691 41 1342 5822
452866 Homo sapiens cDNA FLJ21243 fis, clone R26969 Hs 268016 41 4361 8191
452689 transfernn F33868 Hs 284176 41 4342 8176
409012 DKFZP434I216 protein AL117435 Hs 49725 41 293 2945013
449717 cerebral cell adhesion molecule AB040935 Hs 23954 41 41104111 7989
414172 phosphatidylmositol glycan, class C AW954324 Hs 75790 41 785 5393
428001 ESTs, Moderately similar to Transformm H97428 Hs 219907 41 2389 6576
412970 dual specificity phosphatase 10 AB026436 Hs 177534 4 1 661 6625295
409512 melanoma differentiation associated pro AW979187 Hs 293591 41 354 5057
428778 fibroblast growth factor receptor like AK000530 Hs 193326 41 24732474 6642
444739 Homo sapiens cDNA FLJ12924 fis, clone N N48982 Hs 38034 41 3720 7670
422609 sialidase 1 (lysoso al sialidase) Z46023 Hs 118721 41 1711 6093
418327 paired-like homeodomain transcription f U70370 Hs 84136 41 1217 1218 5729
418932 cadhenπ 4, type 1, R cadhenn (retinal L34059 Hs 89484 40 1285 1286 5777 434408 ESTs AI031771 Hs 132586 40 30537080
412561 lymphocyte-activation gene 3 NM 002286 Hs74011 40 6036045249
408901 hypothetical protein FLJ 10468 AKO~01330 Hs48855 40 2722734997
437202 nuclear transcription factor Y, gamma AA326110 Hs374481 40 32437240
401552 C15001438 gι|7300644|gb|AAF55793 1| (AE 40 4653
435674 ESTs H18063 Hs 13254 40 31447156
430381 1-acylglycerol-3-phosphate O-acyltransf NMJ06411 Hs240534 40 268426856796
417160 proteolipid protein 1 (Pelizaeus-Merzba N76497 Hs355807 40 10865626
428409 ESTs AW117207 Hs98523 40 24386616
453949 heat shock 105kD AU077146 Hs36927 40 44748284
420247 hypothetical protein FLJ20979 AA256930 Hs44680 40 14375895
421508 absent in melanoma 2 NMJ04833 Hs 105115 40 155115525977
453983 ESTs H94997 Hs 16450 40 44768286
424223 putative DNA/chromatin binding motif AJ243706 Hs 143323 40 191519166240
452068 ESTs W76412 Hs57877 40 42828125
419490 granzyme A (granzyme 1 , cytotoxic T-Iym NM 006144 Hs 90708 40 134313445823
447519 ESTs U46258 Hs339665 40 39367844
411492 immunoglobulin superfamily, member 4 T46848 Hs70337 40 5385195
425688 NGFI-A binding protein 2 (ERG1 binding U48361 Hs 159223 40 212421256386
428450 KIAA0175 gene product NM_014791 Hs 184339 40 244324446621
411943 ESTs, Weakly similar to S44608 C02F56 BE502436 Hs7962 40 5625214
425390 protein tyrosine phosphatase, noπ-recep AI092634 Hs 156114 40 20986368
423408 hypothetical protein FLJ11743 AA325517 Hs321046 40 18056161
417933 thy idylate synthetase X02308 Hs82962 40 117011715692
421666 en ot elm 3 AL035250 Hs 1408 40 157415755991
457639 ESTs W02410 Hs205555 40 45588356
430200 geminm BE613337 Hs234896 40 26586777
425172 ESTs AA447729 Hs 12714 40 20626343
406908 gb H sapiens proteiπ-tyrosine kinase ge Z25437 40 77784842
404561 tnchorhmophalangeal syndrome I gene ( 40 4751
407604 collagen, type VIII, alpha 2 AW191962 Hs353001 40 1454891
405411 ENSP00000252213 SODIUM BICARBONATE COTR 40 4781
407856 phosphoprotein associated with GEMs AA045281 Hs266175 40 1704914
438614 KIAA1305 protein AB037726 Hs 288348 40 333833397326
428309 cellular retmoic acid-binding protein M97815 Hs 183650 40 242724286608
428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs337534 40 23936579
448610 nel (chιcken)-lιke 1 NM_006157 Hs21602 39 401940207912
409988 transcription factor AP-2 alpha (activa N27687 Hs334334 38 4015092
409198 H2A histone family, member P L19778 Hs51011 24 3233245036
TABLE 5B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Numbi Accession
406782 00 AA430373 AA968771
406636 00 L12064 L12083 L12065 L12075 L12066 L12085 L12072 L12082 L12081 L12062 L12080
426076 12279581 AW962714 AA369277 AA369278
455813 15155901 BE141577 BE141585 BE141587
426413 372468 T AW954494 AA377823 BG219617 BG195685 BG616269 AI022688
406642 00 AJ245210 AJ245212 AJ245211 AJ245213
455169 11029201 AW860953 AW860967 AW860955 AW862593 AW860963 AW862595 AW860889 BF334678 AW860965 AW860890 AW860905
AW860908 BI031718
TABLE 5C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers "Dunham I et al " refers to the publication entitled
"The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
404854 7143420 Plus 14260-14537
403349 8569773 Minus 167815-168374
402992 7767907 Minus 42137-42515
406367 9256126 Minus 58313-58489
404378 8810489 Minus 133379-133526
401797 6730720 Plus 6973-7118
403404 9438460 Plus 22392-22598,22967-23148
404815 5911819 Minus 64494-64691
404030 7671252 Plus 149362-151749
402888 9930892 Minus 54727-54901
403857 7708910 Minus 2524-3408
405542 9857564 Plus 71331-72183
404240 5002624 Minus 116132-116407,116653-116922
405451 7622517 Minus 145949-146227
403402 9438460 Plus 13943-14086,15552-15845,16211-16483
402474 7547175 Minus 53526-53628,55755-55920,57530-57757
403668 7259739 Plus 39942-40150
403405 9438460 Plus 24174-24296
404977 3738341 Minus 43081-43229
404277 1834458 Minus 91665-91946
400543 9800021 Minus 101471-102209 405104 8077004 Plus 55387-55519
404721 9856648 Minus 173763-174294
401357 9931663 Plus 143295-143425
402994 2996643 Minus 4727-4969
405770 2735037 Plus 61057-62075
404920 6289231 Plus 94213-94389
405372 2078459 Minus 10148-10272,11205-11349,11436-11560,1178
402876 9864669 Plus 5679 6027,7485-7584
400802 8567867 Minus 174571-174856
403130 9211429 Plus 62566-62725
403508 7630896 Plus 5570-5719
401176 9438469 Minus 20475-20734
401552 8099284 Minus 78877-79056
404561 9795980 Minus 69039-70100
405411 3451356 Minus 17503-17778,18021-18290
TABLE 6A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of rhabdomysarcoma AIs divided by the 50th percentile of normal tissue AIs, where the subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
418678 cancer/testis antigen (NY-ES0 1) NM_001327 Hs 87225 200 1269 12705765
429664 POU domain, class 4, transcription fact L20433 Hs 211588 184 26002601 6734
419078 insulinoma associated 1 M93119 Hs 89584 173 1297 12985787
452899 nescient helix loop helix 1 M96739 Hs 30956 170 4367 8196
431727 ESTs AW293464 Hs 162031 153 2814 6889
412719 ESTs AW016610 Hs 816 151 633 5270
419741 ubiquitm earner protein E2-C NM 007019 Hs 9 3002 145 1379 13805850
416836 choiecystokinin D54745 Hs 80247 13 8 1038 5589
452838 preferentially expressed antigen in mel U65011 Hs 30743 13 6 435743588188
452340 ISL1 transcription factor, LIM/homeodom NM 002202 Hs 505 129 431743188155
417308 KIAA0101 gene product H60720 Hs 81892 127 1094 5634
422960 cadhenn 13, H cadheπn (heart) AW890487 Hs 355618 127 1762 6130
414683 hypothetical protein MGC12702 S78296 Hs 76888 126 846847 5444
430294 guanine nucleotide binding protein 4 AI538226 Hs 32976 125 2677 6791
417389 midkiπe (neuπte growth promoting facto BE260964 Hs 82045 123 1109 5647
447377 transcription factor AP-2 alpha X77343 Hs 334334 120 3920 3921 7831
434314 RAB26, member RAS oncogene family BE392921 Hs 3797 120 3042 7072
424411 crystallin, betaA2 NMJ05209 Hs 1 46549 11 194519466262
407168 ESTs R45175 Hs 117183 11 7 116 4868
446921 small inducible cytokine subfamily A (C AB012113 Hs 16530 11 6 387838797797
441290 cholmergic receptor, nicotmic, alpha W27501 Hs 89605 11 3 3507 7482
443184 ESTs AI638728 Hs 135159 11 3 3607 7574
445084 hypothetical protein FLJ14761 H38914 Hs 250848 11 2 3742 7687
417153 collagen, type II, alpha 1 (primary ost X57010 Hs 81343 11 2 1084 10855625
457411 iroquois class homeobox protein IRX2 AW085961 Hs 130093 11 4549 8349
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 107 20992100 6369
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 10 6 1669 16706062
407178 AP-2 beta transcription factor AA195651 Hs 352312 106 118 4870
438703 ESTs AI803373 Hs 31599 103 3348 7333
416854 Purkmje cell protein 4 H40164 Hs 80296 103 1041 5591
417900 CDC20 (cell division cycle 20, S cerev BE250127 Hs 82906 103 1165 5688
413248 hypothetical protein DKFZp547J036 T64858 Hs 380145 101 690 5319
451952 ESTs AL120173 Hs 301663 101 4264 8111
440492 hypothetical protein DKFZp547J036 R39127 Hs 380145 10 1 3469 7448
436481 HSPC150 protein similarto ubiquitm co AA379597 Hs 5199 10 0 3192 7197
423362 myosin XV NM J16239 Hs 1 27561 99 1800 1801 6158
426784 chromogranin A (parathyroid secretory p U03749 Hs 172216 98 2271 22726485
433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 98 292329246977
420092 ESTs AA814043 Hs 88045 97 1415 5877
413278 mterferon-stimulated protein, 15 kDa BE563085 Hs 833 97 695 5322
453857 Ras-induced senescence 1 (RIS1) AL080235 Hs 35861 96 44494450 8266
442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 96 3551 7523
450390 Human DNA sequence from clone RP11-234G N9322 ' Hs 348805 96 4163 8031
429290 neurofila ent, heavy polypeptide (200kC > AF203032 Hs 198760 96 25382539 6692
410687 lysyl oxidase-like 1 U24389 Hs 65436 95 4854865153
442432 hypothetical protein FLJ23468 BE093589 Hs 38178 95 3563 7535
433929 ESTs AI375499 Hs 27379 94 3016 7050
437204 ESTs, Weakly similar to 155214 salivary AL110216 Hs 355961 94 3244 7241
453240 hypothetical protein DKFZp566l133 AI969564 Hs 380132 94 4406 8230
449956 Inhibitor of DNA binding 2, dominant ne AA004852 Hs 180919 93 4122 8000
440210 ESTs AW674562 Hs 122128 93 3462 7441
438091 nuclear receptor subfamily 1, group I, AW373062 Hs 351546 92 3302 7295
411666 neurofilament 3 (150kD medium) AF106564 Hs 71346 9 1 546 5201
418156 nuclear receptor subfamily 1, group I, W17056 Hs 83623 90 1198 5715
450164 ESTs AI239923 Hs 63931 90 4138 8013
410402 similar to mouse Ras, dexamethasone-ind AL022334 Hs 248222 89 458 4595134
413597 ESTs AW302885 Hs 117183 89 732 5349
435652 uncharacteπzed hypothalamus protein HB N32388 Hs 334370 88 3142 7154 432143 Homo sapiens, clone IMAGE 4178394, mRNA AL040183 Hs 123484 88 28456912 441134 cellular retmoic acid-binding protein W29092 Hs 346950 88 35007475 430627 atonal homolog 1 (Drosophila) U61148 Hs 247685 87 271527166816 410366 hypothetical protein AI267589 Hs 302689 87 4575133 438089 nuclear receptor subfamily 1 , group I, W05391 Hs 351546 87 33017294 410467 dachshund (Drosophila) homolog AF102546 Hs 63931 87 4634645137 424687 matrix metalloproteinase 9 (gelatmase J05070 Hs 151738 87 198619876289 453582 hypothetical protein FLJ11937 AW854339 Hs 33476 85 44278247 452363 Homo sapiens, Similar to complement com AI582743 Hs 94953 85 43228159 439671 kinesin family member 5C AW162840 Hs 6641 84 34157398 455601 SRY (sex determining region Y)-box 2 AI368680 Hs 816 84 45078313 423232 leucine nch neuronal protein BE244625 Hs 125742 83 17876149 438831 synapsm II BE263273 Hs 6439 8 3 33577341 432729 hypothetical protein FLJ20285 AK000292 Hs 130732 83 290229036960 408826 Homo sapiens clone HB-2 mRNA sequence AF216Q77 Hs 48376 82 2634990 417160 proteolipid protein 1 (Pelizaeus Merzba N76497 Hs 355807 8 2 10865626 412754 amyloid beta (A4) precursor-like protei AW160375 Hs 74565 82 6365273 440650 Human DNA sequence from PAC 75N13 on ch R44692 Hs 326801 82 34777455 412471 endothelial cell growth factor 1 (plate M63193 Hs 73946 82 5915925239 409893 minichromosome maintenance deficient (S AW247090 Hs 57101 82 3975088 414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 7895397 420783 lectin, galactoside-bmdin , soluble, 7 AI659838 Hs 99923 14785924 443247 c-Myc target JP01 BE614387 Hs 333893 36117578 419236 Homo sapiens cDNA FLJ 11481 fis, clone H AA330447 Hs 135159 13215805 443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 362136227586 400411 Homo sapiens G-protem gamma 8 subunit AF188179 20214625 425256 collapsin response mediator protein 1 BE297611 Hs 155392 79 20746352 422809 hypothetical protein FLJ10549 AK001379 Hs 121028 78 174117426115 406673 major histocompatibility complex, class M34996 Hs 98253 78 90914821 444279 choliπergic receptor, nicotmic, alpha U62432 Hs 89605 77 368836897645 415989 ESTs A1267700 Hs 351201 77 9625530 441390 ESTs AI692560 Hs 355961 77 35167489 407112 ESTs, Weakly similar to ALU7_HUMAN ALU AA070801 Hs 51615 77 1114863 435099 (lap structure specific endonuclease 1 AC004770 Hs 4756 77 310431057123 419086 Kallmanπ syndrome 1 sequence NM-.000216 Hs 8 9591 77 130013015789 424800 MyoD family inhibitor AL035588 Hs 153203 76 200220036300 446051 ephrιn-A3 BE048061 Hs 37054 76 38167744 420460 Homo sapiens clone HB-2 mRNA sequence AA262331 Hs 48376 76 14535907 414945 lymphocyte antigen 6 complex, locus E BE076358 Hs 77667 75 8945477 409142 SMC4 (structural maintenance of chromos AL136877 Hs 50758 75 3123135027 412107 growth factor independent 1 BE242676 Hs 73172 7 5 5705221 444527 small inducible cytokine subfamily A (C NMJ05408 Hs 1 1383 75 370337047657 424468 LIM homeobox protein 3 AF156889 Hs 148427 75 195819596271 413407 inositol polyphosphate phosphatase like AI356293 Hs 75339 74 7135333 449722 cyclin B1 BE280074 Hs 23960 74 41127990 412140 RAB6 interacting, kmesin-like (rabkine AA219691 Hs 73625 74 5735223 423279 ESTs AW959861 Hs 290943 74 17906151 454140 hypothetical protein FLJ10474 Hs 41793 74 449344948301 439979 hypothetical protein FLJ10430 AW600291 Hs 6823 74 34427424 421307 Homo sapiens mRNA, cDNA DKFZp434B0425 ( BE539976 Hs 10330574 15285963 453243 KIAA0441 gene product AB007901 Hs 32511 73 440744088231 430826 POU domain, class 4, transcription fact U10061 Hs 248019 73 273127326828 418375 synaptosomal-associated protein, 25kD NM_003081 Hs 84389 73 122212235732 453597 myo inositol 1-phosphate synthase A1 BE281130 Hs 381118 73 44298249 408915 heptacellular carcinoma novel gene-3 pr NM 116651 Hs 48950 73 2742754998 414117 proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs 355807 73 7775386 452223 hypothetical protein MGC2827 AA425467 Hs 8035 73 43028142 429345 hypothetical protein R11141 Hs 199695 7 2 25486700 444006 type I transmembrane protein Fn14 BE395085 Hs 334762 72 36687627 408562 roundabout (axon guidance receptor, Dro AI436323 Hs 31141 7 2 2404971 450663 nbonuclease HI, large subunit H43540 Hs 25292 72 41798044 448610 nel (chicken) like 1 NM.006157 Hs 2 1602 72 401940207912 416322 pyrrolme 5 carboxylate reductase 1 BE019494 Hs 79217 7 1 9895554 453392 SRY (sex determining region Y) box 11 U23752 Hs 32964 7 1 441644178239 425770 spastic ataxia of Charlevoix-Saguenay ( NM_014363 Hs 1 59492 7 1 213621376393 437036 ESTs AI571514 Hs 133022 7 1 32327231 450447 hypothetical protein P15-2 AF212223 Hs 25010 7 1 416841698036 424001 paternally expressed 10 W67883 Hs 137476 7 1 18826217 443981 KIAA0274 gene product D87464 Hs 10037 7 1 366436657624 443071 complement component 1 , q subcomponent, AL080021 Hs 8986 7 1 35987566 426991 Homo sapiens cDNA FLJ10674 fis, clone N AK001536 Hs 214410 7 1 22946502 431629 interferon, alpha inducible protein (cl AU077025 Hs 265827 70 28036881 432731 fibronectin 1 R31178 Hs 287820 70 29046961 432409 KIAA1575 protein AA806538 Hs 130732 70 28736935 414761 enhancer of zeste (Drosophila) homolog AU077228 Hs 77256 70 8655458 418515 ESTs Weakly similarto CNIR.HUMAN CORN AI568453 Hs 19487 70 12495750 428450 KIAA0175 gene product NM_014791 Hs 1 84339 69 244324446621 445016 reelin U79716 Hs 12246 69 373837397684 421777 HSPC037 protein BE562088 Hs 108196 6 9 15906002 443021 lg superfamily protein AA368546 Hs 8904 6 9 35937561 425274 minichromosome maintenance deficient (m BE281191 Hs 155462 68 20796356 433447 neuronal pentraxin II U29195 Hs 3281 298029817021 414416 hypothetical protein MGC2721 AW409985 Hs 76084 68 8135417 451489 amyloid beta (A4) precursor protein bin NM_005503 Hs 26468 68 423342348088 442285 uncharactenzed hypothalamus protein HT W28729 Hs 374989 68 35547526 435977 brain specific membrane anchored protei AL138079 Hs 5012 68 31667174 407792 putative secreted ligand homologous to AI077715 Hs 39384 68 162 4906
443859 fol statin NM 13409 Hs 9914 68 3651 36527613
444381 hypothetical protein BC014245 BE387335 Hs 283713 68 3697 7652
436608 down syndrome cπtical region protein D AA628980 Hs 192371 68 3205 7207
422363 replication factor C (activator 1) 3 (3 T55979 Hs 115474 67 1673 6065
421362 hypothetical protein FLJ20043 AK000050 Hs 103853 67 1531 15325965
427239 ubiquitm earner protein BE270447 Hs 356512 67 2311 6515
410889 twist (Drosophila) homolog (acrocephalo X91662 Hs 66744 67 501 5025164
428405 cholinergic receptor, nicotimc, alpha Y00762 Hs 2266 67 243624376615
416602 Protein kinase C-bindmg protein NELL2 NM 06159 Hs 367895 67 101 10185575
407619 collageπ, type IX, alpha 2 AL050341 Hs 37165 67 146 1474892
432527 ESTs AW975028 Hs 102754 67 2883 6944
416065 proliferating cell nuclear antigen BE267931 Hs 78996 67 968 5536
425234 ESTs, Weakly similar to I38022 hypothet AW152225 Hs 165909 67 2070 6349
416658 fibπllm 2 (congenital contractura! ar U03272 Hs 79432 67 1020 1021 5577
418399 hypothetical protein FLJ12442 AF131781 Hs 84753 66 1232 12335738
450676 ESTs AI147155 Hs 279727 66 4180 8045
409633 ESTs AW449822 Hs 55200 66 371 5068
419405 ESTs AI377043 Hs 42189 66 1333 5816
437044 differentially expressed in Fancom's a AL035864 Hs 69517 65 3233 7232
435732 leucine πch repeat and death domain co AF229178 Hs 123136 65 314731487159
438076 ESTs W88525 Hs 18816 65 3298 7291
453439 guanine nucleotide binding protein 4 AI572438 Hs 32976 65 4419 8241
410359 ESTs R38624 Hs 106313 65 455 5131
431183 KDEL (Lys Asp Glu-Leu) endoplasmic ret. NM 06855 Hs 250696 64 275627576845
452097 a dismtegπn-like and metalloprotease AB002364 Hs 27916 64 428742888130
450748 ESTs AI733093 Hs 247686 64 4189 8053
409731 thymosm, beta, identified in neuroblas AA125985 Hs 56145 64 386 5080
412577 CD163 antigen Z22968 Hs 74076 64 608 6095252
418113 SRY (sex determining region Y) box 4 AI272141 Hs 83484 64 1194 5711
411789 Adlicaπ AF245505 Hs 72157 64 5535545207
422515 multifunctional polypeptide similar to AW500470 Hs 117950 63 1693 6079
439522 Homo sapiens, clone MGC 15766, mRNA, co AA405968 Hs 58219 63 3404 7387
453139 Human DNA sequence from clone RP11-234G AA330620 Hs 34880563 4394 8220
433036 ESTs AA574091 Hs 105964 63 2929 6981
434284 ankyrm 1, erythrooylic N63745 Hs 183805 63 3041 7071
409799 phosphoseπne phosphatase-like D11928 Hs 76845 63 387 5081
452701 glutamιne-fructose-6-phosphate transamι NM 05110 Hs 30332 63 43454346 8178
424308 minichromosome maintenance deficient (S AW975531 Hs 154443 63 1932 6250
426075 ESTs, Weakly similarto 2109260A B cell AW513691 Hs 270149 63 2170 6417
437696 hypothetical protein dJ37E16 5 Z83844 Hs 5790 63 3281 7274
413995 syntaxm 1A (brain) BE048146 Hs 75671 63 761 5373
421016 transcription factor 3 (E2A immunoglobu AA504583 Hs 101047 63 1497 5937
412014 ESTs, Weakly similarto A46010 X-lmked AI620650 Hs 43761 63 566 5218
457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 63 4561 8359
452056 Homo sapiens, clone IMAGE 4054156, mRNA AW955065 Hs 10115062 4280 8123
436199 hypothetical protein FLJ14503 R38946 Hs 127951 62 3175 7180
427400 hypothetical protein FLJ 11939 AW245084 Hs 94229 62 2325 6525
449052 ESTs AW029507 Hs 161102 62 4062 7946
453041 Homo sapiens cDNA FLJ11918 fis, clone H AI680737 Hs 289068 62 4384 8211
439753 hypothetical protein from EUROIMAGE 216 BE262233 Hs 7423 62 3429 7412
430167 FEV protein Y08976 Hs 234759 62 26552656 6775
451766 ephrιn-B3 NMJ01406 Hs 26988 62 425542568104
456508 ESTs, Weakly similar to AF208855 1 BM 0 AA502764 Hs 123469 62 4521 8325
456534 phospholipase C, beta 3, neighbor pseud X91195 Hs 100623 62 4522 8326
408349 homeo box C10 BE546947 Hs 44276 62 213 4949
429903 cyclin dependent kinase 5, regulatory s AL134197 Hs 93597 62 2616 6746
439668 frizzled (Drosophila) homolog 8 AI091277 Hs 302634 62 3414 7397
431070 transcription factor 19 (SC1) AW408164 Hs 249184 62 2744 6837
410530 ATPase, H transporting, lysosomal (vacu M25809 Hs 64173 61 4694705141
434859 collapsm response mediator protein 5, BE255080 Hs 299315 61 3083 7104
450414 KIAA1716 protein AI907735 Hs 21446 6 1 4165 8033
402994 NM J02463* Homo sapiens myxovirus (infl 6 1 4701
450701 hypothetical protein XP_098151 (leucine H39960 Hs 288467 61 4183 8048
414747 centromere protein F (350/400kD, mitosi U30872 Hs 77204 61 861 8625455
449514 protein predicted by clone 23627 AW970440 Hs 23642 61 4093 7975
440774 ESTs A1420611 Hs 153934 61 3486 7462
418406 cytokeratin 20 X73501 Hs 84905 60 1235 12365740
452319 transducm like enhancer of split 1, ho M99435 Hs 28935 60 431343148152
447414 neuroblastoma (nerve tissue) protein D82343 Hs 74376 60 392439257834
419991 eyes absent (Drosophila) homolog 1 AJ000098 Hs 94210 60 140414055869
432290 Homo sapiens cDNA FLJ10237 fis, clone H AK001099 Hs 274273 60 2862 6926
418322 cyclin dependent kinase inhibitor 3 (CD AA284166 Hs 84113 60 1214 5727
452242 gycosyltraπsferase R50956 Hs 159993 60 4305 8145
427375 metallocarboxypeptidase CPX-1 AL035460 Hs 177536 60 23202321 6522
406634 GDP dissociation inhibitor 1 AA386235 Hs 74576 60 31 4813
418140 microfibrillar-associated protein 2 BE613836 Hs 83551 60 1196 5713
436190 gb Homo sapiens cDNA FLJ10197 fis, cloπ AK001059 Hs 3821 60 317331747179
426509 peπtaxm-related gene, rapidly induced M31166 Hs 2050 60 224322446468
438162 deleted in bladder cancer chromosome re NM_014618 Hs 6090 60 330633077299
414915 myxovirus (influenza) resistance 1, hom NM 02462 Hs 76391 60 8888895473
452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 60 43104311 8150
429415 pracollageπ C-endopeptidase enhancer NMJJ02593 Hs 202097 60 255725586706
409012 DKFZP434I216 protein AL117435 Hs 49725 59 293 2945013
443210 hypothetical protein MGC13168 A1692649 Hs 9451 59 3609 7576
456658 Homo sapiens PAC clone RP4-751H13 from AI660203 Hs 112158 59 4527 8330 414812 monokme induced by gamma interferon X72755 Hs 77367 59 8748755464
424439 ligase I, DNA, ATP-dependent AA579635 Hs 1770 59 1950 6265
441689 ESTs AI123705 Hs 289068 59 3533 7505
415947 mutS (E coli) homolog 2 (colon cancer, U04045 Hs 78934 59 960961 5529
420238 ESTs, Weakly similar to 2109260A B cell AA256783 Hs 12549 59 1436 5894
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 59 3057 7083
414732 minichromosome maintenance deficient (S AW410976 Hs 77152 59 859 5453
410102 ESTs, homologue of PEM 3 [Ciona savigny AW248508 Hs 279727 58 422 5107
443912 ESTs R37257 Hs 184780 58 3657 7618
429163 gb am20a10 s1 Soares_NFL_T_GBC_S1 Homo AA884766 58 2521 6678
435793 KIAA1313 protein AB037734 Hs 4993 58 315231537162
435978 Homo sapiens PR-domain zinc finger prot AF272899 Hs 135118 58 316731687175
422283 CDC45 (cell division cycle 45, S cerevi AW411307 Hs 114311 58 1668 6061
452833 KIAA0124 protein BE559681 Hs 30736 58 4355 8186
409327 collagen, type IX, alpha 3 L41162 Hs 53563 58 341 3425047
400263 Eos Control Hs 75309 58 4613
447733 MAD2 (mitotic arrest deficient, yeast, AF157482 Hs 19400 58 3955 39567860
417115 small nuclear ribonucleoprotein polypep AW952792 Hs 334612 58 1081 5622
444371 forkhead box M1 BE540274 Hs 239 58 3696 7651
453830 ESTs AA534296 Hs 20953 58 4445 8263
419550 KIAA0128 protein, septin 2 D50918 Hs 90998 58 1348 13495827
457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs 32399 58 4543 8344
435141 Recδp, a meiotic recombination and sist AA862498 Hs 4767 58 3108 7126
447499 protocadhenn beta 16 AW262580 Hs 147674 58 3934 7842
427528 minichromosome maintenance deficient (S AU077143 Hs 179565 58 2341 6537
417933 thymidylate synthetase X02308 Hs 82962 58 1170 1171 5692
439963 platelet-activating factor acetylhydrol AW247529 Hs 6793 58 3441 7423
438821 ESTs AA826425 Hs 192375 58 3355 7339
431049 hypothetical protein FLJ22548 similar t AA846576 Hs 103267 58 2743 6836
444783 anilliπ (Drosophila Scraps homolog), ac AK001468 Hs 62180 58 372237237672
415857 Homo sapiens cDNA FLJ11381 fis, clone H AA866115 Hs 127797 58 952 5523
409062 Homo sapiens mRNA, cDNA DKFZp564B182 (fAL157488 Hs 50150 58 301 5018
418478 cyclin dependent kinase inhibitor 2A (m U38945 Hs 1174 57 1245 12465747
440209 neurexin 3 H05049 Hs 247837 57 3461 7440
428342 Homo sapiens cDNA FLJ13458 fis clone P AI739168 Hs 349283 57 2432 6611
407136 Homo sapiens cDNA FLJ11533 fis, clone H T64896 Hs 287420 57 113 4865
406367 NM_022357 Homo sapiens putative metallo 57 4804
428949 hypothetical protein DKFZp434J0617 AA442153 Hs 104744 57 2490 6655
433075 sortilin 1 NM 002959 Hs 351872 57 2936 29376987
428289 complement component 2 M26301 Hs 2253 57 2421 24226603
438915 Williams-Beuren syndrome chromosome reg AA280174 Hs 355711 57 3365 7348
413882 ESTs AA132973 Hs 184492 57 750 5364
449789 hypothetical protein DKFZp566l133 AA004300 Hs 380132 57 4116 7994
418574 M-phase phosphoprotein 9 N28754 Hs 351230 57 1258 5757
425295 ESTs AA431366 Hs 37251 57 2085 6360
407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 57 166 4910
424840 extra spindle poles, S cerevisiae, hom D79987 Hs 153479 57 2011 20126306
448775 nudix (nucleoside diphosphate linked mo i AB025237 Hs 388 57 403640377927
420005 ESTs AW271106 Hs 133294 57 1407 5871
425048 ESTs H05468 Hs 164502 57 2040 6327
412978 homeo box C6 AI431708 Hs 820 57 665 5298
409698 short stature homeobox 2 AF022654 Hs 55967 56 378379 5074
406964 FGENES predicted novel secreted protein M21305 56 87884847
441016 ESTs AW138653 Hs 25845 56 3494 7470
437898 ESTs W81260 Hs 43410 56 3293 7286
446619 secreted phosphoprotein 1 (osteopontm, AU076643 Hs 313 56 3861 7782
414312 ESTs AA155694 Hs 191060 56 800 5407
435708 ESTs AI362949 Hs 6439 56 3146 7158
453665 ESTs, Weakly similar to SFRB_HUMAN SPLI AA626250 Hs 326184 56 4434 8253
438944 KIAA1444 protein AA302517 Hs 92732 56 3368 7351
421506 thymidine kinase 1, soluble BE302796 Hs 105097 56 1550 5976
432562 DKFZP586G1122 protein BE531048 Hs 278422 56 2887 6948
434022 ESTs R18374 Hs 117956 56 3024 7057
428046 ESTs Moderately similar to I38022 hypo AW812795 Hs 337534 56 2393 6579
446021 nbosomal protein L4 BE389213 Hs 286 56 3811 7740
422094 F-box only protein 5 AF129535 Hs 272027 55 1642 1643 6041
447200 Homo sapiens cDNA FLJ14028 fis, clone H BE543146 Hs 281434 55 3899 7815
424837 N-acetyltransferase, homolog of S cere BE276113 Hs 333034 55 2010 6305
406851 major histocompatibility complex, class AA609784 Hs 352392 55 71 4838
432247 ESTs AA531287 Hs 105805 55 2859 6923
451407 fibroblast growth factor 12B AA131376 Hs 343809 55 4230 8085
418216 AF15q14 protein AA662240 Hs 283099 55 1206 5721
434149 hypothetical protein MGC5469 Z43829 Hs 244624 55 3030 7063
426265 ESTs AA421069 Hs 97896 55 2189 6432
428058 ESTs AI821625 Hs 191602 55 2395 6581
414430 ubiquitm carboxyl terminal esterase L1 AI346201 Hs 76118 55 815 5419
450693 ESTs AW450461 Hs 203965 55 4182 8047
419260 protein kinase Njmu R1 H08819 Hs 334851 55 1323 5807
424440 ESTs AA340743 Hs 133208 55 1951 6266
408196 SRY (sex determining region Y) box 22 AL034548 Hs 43627 55 199 2004940
439456 hypothetical protein FLJ20980 AI752409 Hs 109314 55 3400 7383
422871 collagen, type XI, alpha 2 AL031228 Hs 121509 55 1753 17546123
418255 ESTs AW135405 Hs 37251 55 1209 5723
420805 reticulon 1 L10333 Hs 99947 54 1480 1481 5926
448277 hypothetical protein FLJ13044 BE622827 Hs 99486 54 3991 7890
437741 putative transmembrane protein, ho oloi g BE561610 Hs 5809 54 3283 7276 413945 CD14 antigen NM 000591 Hs 75627 54 7587595371
424870 ESTs T15545 Hs 244624 54 2014 6308
425157 phospholipid transfer protein NMJ06227 Hs 283007 54 2057 20586340
429038 seizure related gene 6 (mouse) like AL023513 Hs 194766 54 250425056666
441954 Fanconi anemia, complementation group I G A1744935 Hs 8047 54 3542 7514
409608 cadheπn, EGF LAG seven-pass G-type r ecAF231023 Hs 55173 54 3673685065
443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 54 3656 7617
410342 Fc fragment of IgE, high affinity I, re R31350 Hs 743 54 453 5129
445472 Homo sapiens mRNA for KIAA0293 gene, pa AB006631 Hs 12784 54 377337747711
408096 dihydrofolate reductase BE250162 Hs 83765 54 189 4931
429612 pituitary tumor-transforming 1 AF062649 Hs 252587 54 2586 2587 6726
448103 hypothetical protein FLJ11362 AA968672 Hs 8929 54 3976 7878
436748 collagen, type VI, alpha 2 BE159107 Hs 159263 54 3212 7213
443883 seπne (or cysteme) proteinase inhibit AA114212 Hs 9930 54 3653 7614
433570 ESTs, Weakly similar to S55916 nbosoma AI580053 Hs 109007 54 2988 7027
424905 NIMA (never in mitosis gene a) related NM 002497 Hs 1 53704 54 2022 2023 6315
452106 ESTs AI141031 Hs 21342 54 4289 8131
422799 neurexophilm 4 AI933199 Hs 120911 54 1738 6113
450755 ESTs AA010984 Hs 159464 53 4190 8054
408901 hypothetical protein FLJ10468 AK001330 Hs 48855 53 2722734997
407756 ubiquitm specific protease 18 AA116021 Hs 38260 53 159 4903
423961 penostin (OSF-2os) D13666 Hs 136348 53 1878 18796215
434669 core histone macroH2A22 AF151534 Hs 92023 53 306830697093
446839 mitotic spindle coiled coil related pro BE091926 Hs 16244 53 3873 7793
437162 thyroid hormone receptor coactivatiπg p AW005505 Hs 5464 53 3239 7237
450149 Zic family member 2 (odd paired Drosoph AW969781 Hs 132863 53 4136 8011
423354 calcium channel, voltage dependent, alp AB011130 Hs 127436 53 1798 17996157
452402 peroxisome proliferative activated rece AI138530 Hs 22216 53 4327 8162
401621 NMJ25193 Homo sapiens 3 beta hydroxy-d 53 4656
408212 hypothetical protein AA297567 Hs 43728 53 206 4945
447519 ESTs U46258 Hs 339665 53 3936 7844
446674 solute earner family 4 (aπion exchange AA563892 Hs 350401 53 3868 7788
438086 nuclear receptor subfamily 1, group I, AA336519 Hs 83623 53 3300 7293
432154 ESTs AI701523 Hs 112577 53 2846 6913
424949 core-binding factor, runt domain, alpha AF052212 Hs 153934 53 2030 6321
421508 absent in melanoma 2 NM 004833 Hs 1 05115 53 1551 15525977
457060 beta tubulin l, class VI AA402364 Hs 303023 53 4538 8339
412926 macrophage myπstoylated alanine rich C AI879076 Hs 75061 53 655 5290
456364 Homo sapiens, clone IMAGE 3163559, mRNAAA234315 Hs 58093 53 4520 8324
448966 phosphomositol 3 phosphate binding pro i AW372914 Hs 86149 53 4053 7938
451811 hypothetical protein MGC1136 AA663485 Hs 8719 53 4259 8106
447425 acylphosphatase 1, erythrocyte (commoi ι) AI963747 Hs 18573 53 3927 7836
406663 immunoglobulin heavy constant mu U24683 53 39404818
420596 polymerase (DNA directed), epsilon 2 NMJ02692 Hs 99185 53 1467 14685917
434851 ESTs AA806164 Hs 116502 53 3082 7103
422728 MAD (mothers against decapentaplegic, DAW937826 Hs 103262 52 1729 6107
418827 HT021 BE327311 Hs 47166 52 1275 5770
440700 guanine nucleotide binding protein (G p AW952281 Hs 296184 52 3481 7458
424223 putative DNA/chromatin binding motif AJ243706 Hs 143323 52 191519166240
420301 paired box gene 5 (B cell lineage speci AA767526 Hs 22030 52 1442 5899
425348 cadhenn like 24 AL137477 Hs 155912 52 2091 20926364
406837 immunoglobulin kappa constant R70292 Hs 156110 52 69 4836
432191 hypothetical protein, clone Telethonflt AA043193 Hs 273186 52 2851 6916
409625 sphingomyelm phosphodiesterase 2, neut AI394338 Hs 55235 52 369 5066
410407 carbonic anhydrase IX X66839 Hs 63287 52 460461 5135
439653 hypothetical protein FLJ20373 AW021103 Hs 6631 52 3413 7396
401797 Target Exon 52 4663
443063 ESTs AI031852 Hs 65239 52 3596 7564
415197 hypothetical protein TAJ-alpha D82272 Hs 283615 52 919 5495
426215 stanπiocalcm 2 AW963419 Hs 155223 52 2187 6430
400419 Target AF084545 52 22234626
435124 ESTs AA725362 Hs 75514 52 3107 7125
416140 roundabout (axon guidance receptor, Dro AI918035 Hs 301198 52 978 5545
407719 Homo sapiens mRNA for FLJ00065 protein, AW963866 Hs 44021 52 152 4897
438115 ESTs AI564020 Hs 122014 52 3304 7297
411251 HHGP protein R19774 Hs 22835 52 520 5180
407910 fibronectin leucine rich transmembrane AA650274 Hs 41296 52 180 4922
441362 RAD51 (S cerevisiae) homolog (E coli R BE614410 Hs 23044 52 3512 7486
433332 Homo sapiens clone TCCCTA00151 mRNA seq AI367347 Hs 44898 52 2971 7012
432215 nbonucleotide reductase M1 polypeptide AU076609 Hs 2934 52 2853 6918
417089 Homo sapiens cDNA FLJ21909 fis, clone H52280 Hs 18612 5 1 1077 5619
408495 ESTs W68796 Hs 237731 51 232 4963
417222 hypothetical protein MGC2383 AI525424 Hs 42053 51 1089 5629
428977 cyclm B2 AK001404 Hs 194698 51 2496 6659
414011 asparag e synthetase AA307680 Hs 75692 5 1 766 5377
436679 ESTs, Weakly similar to unnamed protein AI127483 Hs 120451 51 3210 7211
431958 cadhenn 3, type 1, P-cadhenπ (placent X63629 Hs 2877 5 1 283428356904
422997 DNA replication factor BE018212 Hs 122908 51 1766 6133
425322 protein kinase, DNA-activated, catalyti U63630 Hs 155637 51 208920906363
432383 Homo sapiens cDNA FLJ20137 fis clone C AK000144 Hs 274449 51 2868 6931
424825 procollagen-lysme, 2 oxoglutarate 5 di AF207069 Hs 153357 5 1 20052006 6302
423897 DKFZP434N178 protein AB033062 Hs 134970 51 1863 18646205
407103 hypothetical protein MGC13170 AA424881 Hs 256301 51 110 4862
422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 51 1734 6110
431797 hypothetical protein FLJ20280 BE169641 Hs 270134 5 1 2822 6896
428752 ESTs AI962660 Hs 98788 51 2469 6639 407192 gb af12e02 s1 Soares_testιs_NHT Hom > saAA60920C ) Hs 366318 51 119 4871
435080 hypothetical protein FLJ14428 AI831760 Hs 155111 51 3103 7122
428479 cell division cycle 2, G1 to S and G21 Y00272 Hs 334562 51 24472448 6623
427820 inhibitor of DNA binding 2, dominant ne BE222494 Hs 180919 51 2374 6563
403857 Target Exon 5 1 4730
448111 interferon-induced protein with tetratr AA053486 Hs 20315 5 1 3978 7880
416908 coagulation factor XIII, A1 polypeptide AA333990 Hs 80424 5 1 1044 5594
428317 ESTs AW022609 Hs 50745 5 1 2431 6610
434349 πeurobeachin NM 015678 Hs 3 821 5 1 30453046 7074
451752 KIAA1171 protein AB032997 Hs 353087 5 1 42524253 8102
414132 ESTs AI801235 Hs 48480 50 778 5387
404208 C6001282 gι|4504223|ref|NP_000172 1| gl 50 4740
444565 ESTs W32889 Hs 154329 50 3707 7659
426919 ELAV (embryonic lethal, abnormal vision AL041228 Hs 166109 50 2284 6495
414245 WAS protein family, member 1 BE148072 Hs 75850 50 791 5399
447217 neuropilm 2 BE465754 Hs 17778 50 3904 7819
434629 glioma amplified sequence 41 AA789081 Hs 4029 50 3064 7090
431689 UDP-Gal betaGlcNAc beta 1,3 galactosylt AA305688 Hs 267695 50 2810 6886
421875 ESTs AA299607 Hs 98969 50 1606 6016
420164 ESTs AW339037 Hs 349096 50 1423 5884
426788 SWI/SNF related, matrix associated, act U66615 Hs 172280 50 227322746486
436574 ESTs AW293527 Hs 126465 50 3202 7204
415052 mesenchyme homeo box 2 (growth arrest-s NM_005924 Hs 77858 50 9049055485
406868 immunoglobulin heavy constant gamma 3 ( AA505445 Hs 300697 50 72 4839
433285 ESTs AW975944 Hs 237396 50 2967 7008
412446 ESTs AI768015 Hs 352375 50 586 5235
404030 NM_015669* Homo sapiens protocadhenn b 50 4735
414359 cadhenn 11, type 2, OB cadhenn (osteo M62194 Hs 75929 50 808 5413
412507 EphA4 L36645 Hs 73964 50 5965975243
448524 hypothetical protein DKFZp762K2015 AB032948 Hs 21356 50 401240137908
420397 ceπtrasomal protein 1 NMJ07018 Hs 97437 50 1449 5904
419488 nucleophosmin/nucleoplasmin 3 AA316241 Hs 90691 50 1342 5822
459305 ESTs AW007781 Hs 249858 50 4591 8387
429138 NS1-bιπdιng protein AB020657 Hs 197298 50 251525166674
453511 AP-2 beta transcription factor AL031224 Hs 33102 50 442244238244
443780 activating transcription factor 5 NM 012068 Hs 9754 50 364336447606
415701 gamma glutamyl hydrolase (conjugase, fo NM_003878 Hs 78619 50 940941 5514
453818 hypothetical protein FLJ13449 BE256832 Hs 10711 50 4443 8261
449230 melanoma cell adhesion molecule BE613348 Hs 356392 50 4074 7956
408161 hypothetical protein MGC3032 AW952912 Hs 300383 50 195 4937
427337 Fc fragment of IgG low affinity lllb, Z46223 Hs 176663 50 231823196521
453271 ESTs AA903424 Hs 6786 50 4409 8232
436291 protein regulator of cytokinesis 1 BE568452 Hs 344037 50 3180 7185
436477 ESTs AA719989 Hs 107894 50 3191 7196
427747 serme/threoniπe kinase 12 AW411425 Hs 180655 49 2365 6557
418241 LIM domain only 1 (rhombotm 1) M26682 Hs 1149 49 1207 12085722
458692 ESTs BE549905 Hs 231754 49 4579 8376
428865 BarH like homeobox 1 BE544095 Hs 164960 49 2485 6651
432715 ESTs, Weakly similarto KIAA1074 protei AA247152 Hs 44566 49 2901 6959
437608 ESTs, Weakly similar to ALU1 HUMAN ALU AA761605 Hs 292308 49 3274 7268
429493 ESTs AL134708 Hs 145998 49 2573 6717
424408 collagen, type V, alpha 1 AI754813 Hs 146428 49 1943 6260
424624 Ca2+dependent activator protein for sec AB032947 Hs 151301 49 1978 19796283
411263 kinesm-like 6 (mitotic centromere asso BE297802 Hs 69360 49 523 5182
417084 ESTs H08370 Hs 57937 49 1076 5618
423811 homeo box C4 AW299598 Hs 50895 49 1854 6198
446142 ESTs AI754693 Hs 145968 49 3820 7748
413199 ELAV (embryonic lethal, abnormal vision M62843 Hs 75236 49 6876885317
434175 ESTs AW979081 Hs 165469 49 3032 7065
423673 matrix metalloproteinase 12 (macrophage BE003054 Hs 1695 49 1837 6186
422938 centromere protein A (17kD) NM 001809 Hs 1 594 49 1759 17606128
448498 ESTs AA418276 Hs 375003 49 4007 7904
454033 homeo box HB9 AF107457 Hs 37035 49 4483 8292
414809 transfemn receptor (p90, CD71) AI434699 Hs 77356 49 873 5463
424415 enolase 2, (gamma, neuronal) NM 001975 Hs 1 46580 49 1947 1948 6263
410711 KIAA0318 protein AB002316 Hs 65746 49 4894905155
452724 cyclin E2 R84810 Hs 30464 49 4347 8179
419585 actin like 6 T08459 Hs 259831 49 1359 5833
439453 thyroid hormone receptor mteractor 13 BE264974 Hs 6566 49 3399 7382
434355 ESTs AA630865 Hs 186556 49 3049 7076
418203 CDC28 protein kinase 2 X54942 Hs 83758 49 1202 12035719
430552 nuclear autoantigenic sperm protein (hi AA176374 Hs 243886 49 2709 6812
424954 tumor protein p53 (Li-Fraumem syndrome NMJ00546 Hs 1 846 49 2031 20326322
446291 interferon, gamma-mducible protein 30 BE397753 Hs 14623 48 3833 7760
448381 Homo sapiens mRNA, cDNA DKFZp434A1010 ( D61580 Hs 21036 48 3996 7895
453884 KIAA0186 gene product AA355925 Hs 36232 48 4460 8274
427407 ADP-nbosyltransferase (NAD, poly (ADP- BE268649 Hs 177766 48 2326 6526
433202 KIAA1465 protein AB040898 Hs 233335 48 2951 29526998
417911 chaperonin containing TCP1 , subunit 6A AA333387 Hs 82916 48 1166 5689
453883 cofactor required for Sp1 transcription AI638516 Hs 347524 48 4459 8273
406698 major histocompatibility complex, class X03068 Hs 73931 48 51 524824
437007 ESTs, Weakly similar to I38022 hypothet AA741300 Hs 202599 48 3230 7229
414341 KIAA0182 protein D80004 Hs 75909 48 804805 5410
452908 neuronal She adaptor homolog AB001451 Hs 30965 48 43694370 8198
407811 cysteine knot superfamily 1, BMP antago AW190902 Hs 40098 48 164 4908
446681 kendπn AJ003624 Hs 15896 48 3869 7789 448663 hypothetical protein MGC14797 BE614599 Hs 356501 4023 7915 409529 Cdc42guanine exchangefactor(GEF) 9 AB007884 Hs 54697 3553565058 406687 matπxmetalloproteinase 11 (stromelysi M31126 Hs 352054 49504823 401827 Target Exon 4664 416801 sal (Drosophιla)-tιke 2 X98834 Hs 79971 10325585 409125 axonal transport of synaptic vesicles R17268 Hs 343567 3085024 407785 ESTs, Weakly similarto A43932 mucm 2 AW207285 Hs 98279 1604904 400262 Eos Control Hs 75309 4612 424878 ESTs H57111 Hs 221132 20176311 411089 cell division cycle 2-lιke 1 (PITSLRE p AA456454 Hs 214291 5135173 450377 KIAA1265 protein AB033091 Hs 355925 416041618029 428293 solute carrier family 1 (neutral ammo BE250944 Hs 183556 24246605 416111 chromatin assembly factor 1, subumtA AA033813 Hs 79018 9755542 411296 growth suppressor 1 BE207307 Hs 10114 5245183 405770 NM-.002362 Homo sapiens melanoma antigen 4796 436252 Homo sapiens cDNA FLJ 11562 fis, clone H AI539519 Hs 142827 31797184 407871 ESTs AA045368 Hs 98317 1744917 421524 GDNF family receptor alpha 1 AA312082 Hs 105445 15565980 413670 hypothetical protein, expressed in oste AB000115 Hs 75470 7357365352 410261 schwannomin interacting protein 1 AF145713 Hs 61490 4394405119 433487 histone deacetylase 2 U31814 Hs 3352 298329847023 431019 forkhead box GIB NM_005249 Hs 2714 274027416834 447321 Homo sapiens cDNA FLJ14028 fis, clone H AW271217 Hs 281434 48 39157827 425308 receptor tyrosine kinase like orphan re M97639 Hs 155585 208720886362 433013 axin 2 (conductin, axil) AI697890 Hs 127337 29276979 419682 paired like homeodomaiπ transcription f H13139 Hs 92282 13685841 431863 spmdlin AA188185 Hs 289043 28296901 406311 NM_021979* Homo sapiens heat shock 70kD 4803 405754 Target Exon 4795 424078 paternally expressed 3 AB006625 Hs 139033 189318946225 423011 adrenergic, alpha-2C-, receptor NMJJ00683 Hs 1 23022 176717686134 458933 RAN binding protein 1 AI638429 Hs 24763 45848381 435523 membrane spanning 4-domaιns, subfamily T62849 Hs 11090 31317147 453990 ESTs AW014847 Hs 233331 44788288 408539 fibulm 1 AA421528 Hs 349607 2374968 417944 collagen, type V, alpha 2 AU077196 Hs 82985 11725693 400235 NM 305336 Homo sapiens high density lip Hs 177516 4604 410868 Homo sapiens cDNA FLJ11490 fis, clone H T06529 Hs 98518 5005163 439452 B cell CLL/lymphoma 11B (zinc finger pr AA918317 Hs 57987 33987381 451987 Homo sapiens cDNA FLJ 14967 fis, clone T AA815092 Hs 77554 42678114 410781 ESTs AI375672 Hs 165028 4955159 458207 U2 small nuclear ribonucleoprotein auxi T28472 Hs 655 45698366 448633 tubulm, gamma 1 AA311426 Hs 21635 40217913 426287 calpam 6 AF029232 Hs 169172 219421956436 430280 interleukin 7 receptor AA361258 Hs 237868 26736787 423449 ESTs AI497900 Hs 57937 18086164 414034 early development regulator 1 (homolog U89277 Hs 305985 7717725381 443715 cyclin E1 AI583187 Hs 9700 36387601 412006 ESTs AW451618 Hs 380683 5655217 420162 cyclin dependent kinase 4 BE378432 Hs 95577 14225883 408660 ESTs, Moderately similar to PC4259 ferr AA525775 Hs 89040 2474977 427701 nuclear autoantigenic sperm protein (hi AA411101 Hs 243886 23626555 410006 eukaryotic translation initiation facto AW732308 Hs 57783 4055095 411773 protease, seππe, 21 (testisin) NM-006799 Hs 72026 5515525206 437597 SCG10 like protein AA730767 Hs 285753 32737267 458079 Homo sapiens similar to RIKEN cDNA 2810 AI796870 Hs 381220 45668363 425801 gb HSG14H051 normalized infant brain CD Z43151 Hs 343666 21446397 428392 secretory granule, neuroeπdocπne prate H10233 Hs 2265 24346613 443623 complement component 1, q subcomponent, AA345519 Hs 9641 36317594 443802 KIAA1291 protein AW504924 Hs 9805 36477609 449267 ESTs AI638640 Hs 220624 40777959 436703 RNA binding motif protein, X chromosome AW880614 Hs 374352 32117212 400991 Target Exon 4641 442573 branched chain aminotransferase 1, cyto H93366 Hs 7567 35707541 450296 hepatocyte growth factor-regulated tyro AL041949 Hs 24756 41538023 411962 gb zk85d12 r1 Soares_pregnant_uterus_Nb AA099050 5635215 440516 cadhenn 2, type 1, N cadhenn (πeurona S42303 Hs 161 347234737451 429024 complement dq tumor necrosis factor-re AI652297 Hs 119302 25026664 414561 Homo sapiens ammo acid transport syste A1064813 Hs 195155 8315432 402992 Target Exon 4700 417312 leukemia associated phosphoprotein p18 AW888411 Hs 250811 10955635 437437 hypothetical protein DKFZp762L0311 AA226869 Hs 351623 32627257 450534 KIAA0470 gene product AI570189 Hs 25132 41758040 429183 KIAA0704 protein AB014604 Hs 197955 252625276681 421707 lectomedιn-2 NM_014921 Hs 1 07054 158115825995 433159 kmesin-like protein 2 AB035898 Hs 150587 294729486996 408949 putative πbonuclease III AF189011 Hs 49163 2802815003 407366 gb Homo sapiens cιg33 mRNA, partial seq AF026942 Hs 17518 1374885 442932 bromodomain adjacent to zinc finger dom AA457211 Hs 8858 35917559 450336 Homo sapiens cDNA FLJ23296 fis, clone AA046814 Hs 288928 41558025 448044 gb tk13e01 x1 NCI_CGAP_Lu24 Homo sapien AI458682 39727874 445564 KIAA1034 protein AB028957 Hs 12896 378437857718 450356 KIAA1674 BE149824 Hs 132888 41568026 406137 NM_000179* Homo sapiens mutS (E coli) 4802 423731 gb EST06706 Infant Brain Bento Soares T08814 Hs 31599 18396188 425003 apunnic/apyrimidinic endonuclease(APEX AF119046 Hs 154149 203820396326 405268 ENSP00000223174* KIAA0783 PROTEIN 46 4776 408989 KIAA0746 protein AW361666 Hs 49500 46 290 5010 426400 Homosapiens clone 25121 neuronalolfac M78361 Hs 169743 46 2218 6452 423419 ESTs R55336 Hs 23539 46 1806 6162 453753 ubiquitm specific protease 1 BE252983 Hs 35086 46 4437 8256 439070 ESTs AI733278 Hs 7621 46 3375 7358 426095 ESTs AI278023 Hs 89986 46 2172 6419 406076 Homo sapiens mRNA, cDNA DKFZp547P134 (f 46 4800 408393 ESTs AW015318 Hs 143509 46 219 4953 439246 membrane-associated tyrosine- and threo AI498072 Hs 351474 46 3386 7369 435013 NMJ20142 Homo sapiens NADH ubiqumone H91923 Hs 110024 46 3096 7115 408190 ATPase, Class I, type 8B, member 2 AB032963 Hs 43577 46 197 1984939 426110 replication factor C (activator 1) 1 (1 NMJ02913 Hs 1 66563 46 217421756421 420058 Homo sapiens cDNA FLJ10561 fis, clone N AK001423 Hs 94694 46 1411 5874 418045 ESTs AI972919 Hs 118837 46 1183 5701 424005 vang (van gogh, Drosophila) like 2 AB033041 Hs 137507 46 1883 18846218 416209 MAD2 (mitotic arrest deficient, yeast, AA236776 Hs 79078 46 982 5549 453905 LIM domain kinase 1 NM J02314 Hs 3 6566 46 446244638276 429986 sine oculis homeobox (Drosophila) homol AF092047 Hs 227277 46 263226336759 414706 KIAA0097 gene product AW340125 Hs 76989 46 854 5449 435832 Bruno (Drosophila) -like 4, RNA binding AA425688 Hs 41641 46 3155 7164 429574 hypothetical protein MGC861 BE268321 Hs 208912 46 2580 6722 424192 P311 protein U30521 Hs 142827 46 1911 19126238 432101 EphA3 AI918950 Hs 123642 46 2841 6909 403650 dynem, cytoplasmic, light polypeptide 46 4726 426118 polymerase (DNA directed), epsilon AF128542 Hs 166846 46 217621776422 435232 cyclin dependent kinase inhibitor 2C (p NM_001262 Hs 4854 45 311431157132 452017 prostate cancer associated protein 7 AF109302 Hs 27495 45 42708117 453922 budding uninhibited by benzimidazoles 1 AF053306 Hs 36708 45 446744688279 423853 slit (Drosophila) homolog 1 AB011537 Hs 133466 45 185518566199 442904 thymopoietin AW575008 Hs 11355 45 35887556 420911 0 linked N-acetylglucosamme (GlcNAc) t U77413 Hs 100293 45 149114925934 438833 ESTs BE612940 Hs 88252 45 33587342 447284 hypothetical protein FLJ10204 AK001066 Hs 18029 45 391239137825 452732 Homo sapiens, clone IMAGE 3535294, mRNA BE300078 Hs 80449 45 43488180 444170 ESTs AW613879 Hs 102408 45 36837640 435256 cytokine like protein C17 AF193766 Hs 13872 45 311631177133 422239 SMT3 (suppressor of iftwo 3, yeast) h AI878922 Hs 180139 45 16626057 406836 immunoglobulin kappa constant AW514501 Hs 156110 45 684835 448985 carbonic anhydrase XI AA324885 Hs 22777 45 40547939 404632 NM_022490 Homo sapiens hypothetical pro 45 4754 410768 Homo sapiens clone 23700 mRNA sequence AF038185 Hs 66187 45 4945158 434862 ESTs AA652272 Hs 197320 45 30847105 448772 L-kynurenme/alpha-aminoadipate aminotr AW390822 Hs 380762 45 40357926 418565 phosphoinositol 3-phosphate-bιndιng pro AK001529 Hs 86149 45 125612575756 418607 KIAA1402 protein AL137426 Hs 86392 45 12605759 429455 CD209 antigen AI472111 Hs 278694 45 25636710 447478 fibronectin type 3 and SPRY domain cont BE618843 Hs 28144 45 39327840 416640 neuron-specific protein BE262478 Hs 13406 45 10195576 452792 KIAA1344 protein AB037765 Hs 30652 45 435143528183 423181 ESTs AA323415 Hs 278385 45 17796144 444664 map kinase phosphatase-like protein MK- N26362 Hs 11615 45 37117663 429320 ESTs, Weakly similarto I78885 seπne/t AA449838 Hs 119334 45 25456697 422575 hypothetical protein FLJ20539 AK000546 Hs 118552 45 170517066089 438293 stromal antigen 2 L08437 Hs 8217 45 33147305 453096 ESTs AW294631 Hs 351270 45 4391 8217 452277 KIAA1223 protein AL049013 Hs 28783 45 43088148 424927 hypothetical protein C321 D24 AW973666 Hs 153850 45 20296320 417576 phosphoπbosylglycinamide formyltransfe AA339449 Hs 82285 45 11345662 440510 ESTs, Weakly similar to ISHUSS protein H08427 Hs 309165 45 34717450 430066 signal recognition particle 72kD AI929659 Hs 237825 45 26476769 422382 KIAA0166 gene product D79988 Hs 115778 45 167416756066 452461 transcription factor N78223 Hs 108106 45 43338167 422684 H2A histone family, member Z BE561617 Hs 119192 45 17266105 416980 high-mobility group (nonhistone chromos AA381133 Hs 80684 45 10545601 414907 polo (Drosophia) like kinase X90725 Hs 77597 45 8868875472 433706 ESTs AW947250 Hs 151604 45 30017037 417777 ESTs, Weakly similar to I78885 seπne/t AI823763 Hs 7055 45 11565679 417731 polymerase (DNA directed), delta 3 D26018 Hs 82502 45 115211535676 447417 KIAA1602 protein AW732858 Hs 143067 45 39267835 421302 neuntin T34462 Hs 103291 45 15275962 456940 ESTs H46986 Hs 31861 45 45348336 447250 protein phosphatase 1G (formerly 2C), AI878909 Hs 17883 45 39067821 409139 ESTs, Highly similarto IRX1_HUMAN IROQ AI681917 Hs 3321 45 3115026 405326 Target Exon 45 4777 400340 homeo box 11-lιke 2 AJ223798 45 12134621 433149 hypothetical protein HES6 BE257672 Hs 42949 45 29466995 431301 ESTs AA502384 Hs 151529 45 27736858 419131 ESTs AA406293 Hs 109526 45 13065794 412314 downstream of G protein coupled recept AA825247 Hs 356084 45 5815230 414175 hypothetical protein DKFZp761 D112 AI308876 Hs 103849 45 7865394 431830 small inducible cytokine subfamily A (C Y16645 Hs 271387 45 282728286900 438937 ESTs AW952654 Hs 73964 45 33677350 418199 ESTs AA884555 Hs 86603 45 12015718 440080 ESTs AW051597 Hs 143707 45 34497431 441020 ESTs W79283 Hs 35962 45 34957471 443725 growth arrest and DNA-damage-mducible, AW245680 Hs 9701 45 3639 7602
425219 cytosolic ovarian carcinoma antigen 1 AF207881 Hs 155185 45 206720686347
422128 gb QV0-OT0033 010400-182-a07 OT0033 Hom AW881145 Hs 6456 45 1650 6047
454075 Kruppel like zinc finger protein GLIS2 R43826 Hs 16313 45 4489 8297
412432 ESTs AA126311 Hs 9879 44 585 5234
406672 major histocompatibility complex, class M26041 Hs 198253 44 43444820
442328 ESTs, Weakly similar to ALU4_HUMAN ALU AI952430 Hs 150614 44 3556 7528
414883 CDC28 protein kinase 1 AA926960 Hs 348669 44 885 5471
413004 interleukin enhancer binding factor 2, T35901 Hs 75117 44 667 5300
424394 RNA binding motif protein, X chromosome BE277024 Hs 146381 44 1941 6258
454561 hepatitis delta antigen interacting pro AI984144 Hs 66713 44 4502 8308
420129 ESTs AA255760 Hs 122994 44 1417 5879
424410 ESTs W79027 Hs 271762 44 1944 6261
411562 hypothetical protein DKFZp586E1923 AL050201 Hs 70769 44 541 5198
422516 multifunctional polypeptide similar to BE258862 Hs 117950 44 1694 6080
452160 cysteine sulfinic acid decarboxylase-re BE378541 Hs 355568 44 4292 8134
412659 oifactomedin related ER localized prate AW753865 Hs 74376 44 627 5265
439239 ESTs AI031540 Hs 235331 44 3385 7368
407896 Zic family member 1 (odd paired Drosoph D76435 Hs 41154 44 176 1774919
408805 vaccinia related kinase 1 H69912 Hs 48269 44 262 4989
414839 DNA (cytosine 5-)-methyltransferase 1 X63692 Hs 77462 44 880881 5467
424451 protein tyrosine phosphatase, non-recep M83738 Hs 147663 44 1955 19566269
425368 cullin 4B AB014595 Hs 155976 44 209620976367
425159 carbamoyl phosphate synthetase 2, aspar NM 004341 Hs 154868 44 205920606341
422795 KIAA1283 protein AB033109 Hs 375610 44 1736 17376112
414725 ring finger protein 21 , interferon-resp AA769791 Hs 350518 44 858 5452
422244 karyopheπn (importin) beta 3 Y08890 Hs 113503 44 1665 16666059
454060 ephnπ-A3 U14187 Hs 37054 44 448544868294
416507 transcription factor Dp-1 AL045364 Hs 79353 44 1009 5569
430439 DKFZP434B061 protein AL133561 Hs 380155 44 269526966803
429656 neurofilament, light polypeptide (68kD) X05608 Hs 211584 44 259825996733
420174 ESTs AI824144 Hs 199749 44 1427 5887
420440 mammaglobιn 2 NM 002407 Hs 97644 44 1450 1451 5905
433211 MARK H11850 Hs 12808 44 2955 7000
421102 protocadhenn beta 6 AI470093 Hs 283085 44 1506 5945
450746 general transcription factor II, i D82673 Hs 278589 44 4187 8051
414733 minichromosome maintenance deficient (S BE514535 Hs 77171 44 860 5454
426512 Meιs1 (mouse) homolog AW511656 Hs 170177 44 2245 6469
414760 chromobox homolog 1 (Drosophila HP1 bet BE298063 Hs 77254 44 864 5457
434256 ESTs AI378817 Hs 191847 44 3036 7068
450553 hypothetical protein MGC3232 AW850613 Hs 8715 44 4176 8041
449433 ESTs, Weakly similar to S26650 DNA-bmd AI672096 Hs 9012 44 4086 7968
430027 KIAA0980 protein AB023197 Hs 227743 44 2639 26406763
402861 Wilms' tumour 1-assocιatιng protein 44 4695
449989 multiple endocrine πeoplasia I U93237 Hs 240443 44 412441258002
424616 intercellular adhesion molecule 5, tele U72671 Hs 151250 44 1975 1976 6281
414528 ESTs AA148950 Hs 188836 44 828 5429
414133 ESTs AW022188 Hs 109526 43 779 5388
411893 ESTs R82845 Hs 273789 43 558 5211
410099 KIAA0036 gene product AA081630 Hs 167 43 421 5106
422565 singed (Drosophila) like (sea urchin fa BE259035 Hs 118400 43 1701 6086
410054 Homo sapiens cDNA FLJ23005 fis, clone AL120050 Hs 58220 43 413 5101
437330 Homo sapiens mRNA, cDNA DKFZp761J1112 ( AL353944 Hs 50115 43 3253 7250
457986 Homo sapiens, clone IMAGE 4299555, mRNA AA781745 Hs 126920 43 4565 8362
447660 ESTs AW160386 Hs 163667 43 3946 7853
412800 polymerase (DNA directed), delta 2, reg AW950852 Hs 74598 43 644 5281
409326 choreoacanlhocytosis gene, KIAA0986 pro AK000273 Hs 53542 43 340 5046
437623 chromosome condensation-related SMC-ass D63880 Hs 5719 43 327532767269
426990 Homo sapiens mRNA for KIAA1750 protein, AL044315 Hs 173094 43 2293 6501
405387 NM_022170* Homo sapiens Williams-Beuren 43 4779
413644 ESTs, Weakly similarto Z195JUMAN ZINC BE154910 Hs 278793 43 733 5350
457313 transcriptional coactivator AF047002 Hs 241520 43 454445458345
416084 deoxythymidylate kinase (thymidylate ki L16991 Hs 79006 43 9729735540
429150 smoothened (Drosophila) homolog AF120103 Hs 197366 43 251925206677
453028 RecQ protein-like 4 AB006532 Hs 31442 43 4381 3828209
425776 parathyroid hormone receptor 2 U25128 Hs 159499 43 21382139 6394
433895 mitogen-activated protein kinase kinase AI287912 Hs 3628 43 3014 7048
435554 early B-cell factor AF208502 Hs 32425 43 313631377150
419356 hypothetical protein FLJ22316 A1656166 Hs 7331 43 1332 5815
452744 Homo sapiens mRNA, cDNA DKFZp434E082 (f AI267652 Hs 24610743 4350 8182
409703 2'-5'-olιgoadenylate synthetase 3 (100 NM 006187 Hs 56009 43 381 3825076
408847 ESTs AW290997 Hs 190153 43 268 4993
436114 ESTs, Highly similar to NRG3 HUMAN PRO- AA778232 Hs 19515 43 3171 7177
425870 ESTs R13406 Hs 56782 43 2153 6405
433411 RNA binding motif protein 4 AI658666 Hs 352381 43 2975 7016
443123 putative transcription regulation nude AA094538 Hs 272808 43 3603 7570
413431 ubiquitm conjugating enzyme E2N (homol AW246428 Hs 75355 43 715 5335
414136 SMC2 (structural maintenance of chromos AA812434 Hs 119023 43 780 5389
443823 hypothetical protein BE089782 Hs 9877 43 3649 7611
424560 protein predicted by clone 23733 AA158727 Hs 150555 43 1972 6279
445139 synaptotagmm XIII AB037848 Hs 12365 43 3746 37477691
403668 Target Exon 43 4727
412672 chromodomain helicase DNA binding prate AA158910 Hs 74441 43 628 5266
410268 six transmembrane epithelial antigen of AA316181 Hs 61635 43 441 5120
422175 ESTs, Highly similar to T00391 hypothet N79885 Hs 6382 43 1657 6053
440001 ESTs AI740721 Hs 128292 43 3445 7427 454104 hypothetical protein MGC2555 BE275031 Hs 158210 43 4491 8299
417588 gb HSC22D091 normalized infant brain cD Z44510 43 1135 5663
412046 RAS-related on chromsome 22 Y07847 Hs 73088 43 5675685219
400295 A19056871L-BT095-190199-019 BT095 Homo W7283Ϊ i Hs 348419 43 6 4617
438407 eukaryotic translation initiation facto A1457122 Hs 129673 43 3320 7310
420759 Homo sapiens cDNA FLJ 11381 fis, clone H T11832 Hs 127797 43 1476 5922
442404 ESTs AI733500 Hs 124370 43 3558 7530
421878 Homo sapiens cDNA FLJ11643 fis, clone H AA299652 Hs 111496 43 1607 6017
436420 ESTs AA443966 Hs 31595 43 3187 7192
421040 ESTs AA715026 Hs 135280 43 1498 5938
414242 dolichyl-phosphate (UDP-N-acetylglucosa AA749230 Hs 143509 43 790 5398
427961 ESTs AW293165 Hs 143134 43 2388 6575
436251 nucleolar protein (KKE/D repeat) BE515065 Hs 296585 43 3178 7183
424026 nbosomal protein L34 pseudogene 1 AI798295 Hs 137576 43 1888 6221
423803 PDZ-73 protein NM 005709 Hs 1 32945 43 185218536197
418661 E2F transcription factor 3 NM 001949 Hs 1 189 43 1264 12655762
454340 gb PMO HT0339-081199-001-h05 HT0339 Hom AW382767 Hs 12212843 4496 8303
443950 epithelial membrane protein 3 NM 001425 Hs 9999 43 3660 3661 7621
448057 RAB39 BE300105 Hs 301853 43 3973 7875
402260 NM 001436* Homo sapiens fibπllann (FB 43 4676
412651 ESTs AA115333 Hs 107968 43 625 5263
421846 protein kinase C substrate 80K-H AA017707 Hs 1432 43 1601 6012
439053 chaperonin containing TCP1, subunit 2 ( BE244588 Hs 6456 43 3374 7357
416565 eπdoplasmic reticulum resident protein AW000960 Hs 44970 43 1015 5573
434792 ESTs AA649253 Hs 132458 43 3075 7099
439512 Homo sapiens, clone IMAGE 3163559, mRNA AA418287 Hs 58093 43 3403 7386
426867 ESTs AA460967 Hs 22668 43 2282 6493
443674 ESTs AI081330 Hs 40510 43 3635 7598
431374 CTP synthase BE258532 Hs 251871 43 2778 6862
428309 cellular ret oic acid-binding protein M97815 Hs 183650 43 24272428 6608
452046 KIAA0802 protein AB018345 Hs 27657 43 42754276 8120
413273 stem-loop (histone) binding protein U75679 Hs 75257 43 6936945321
429984 hypothetical protein FLJ21617 AL050102 Hs 227209 43 26302631 6758
453880 ESTs, Weakly similar to 138022 hypothet AI803166 Hs 135121 43 4458 8272
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 43 1162 5685
427495 Homo sapiens cDNA FLJ 11333 fis, clone P AI799104 Hs 178705 43 2335 6533
417061 Homo sapiens cDNA FLJ12033 fis, clone H AI675944 Hs 188691 43 1068 5612
446849 cleavage and polyadenylation specific f AU076617 Hs 16251 42 3874 7794
400250 Eos Control Hs 3352 42 4608
429918 ESTs AW873986 Hs 119383 42 2619 6748
448390 hypothetical protein AL035414 Hs 21068 42 3999 7897
433234 KIAA1495 protein AB040928 Hs 65366 42 2961 29627005
412795 special AT-nch sequence binding protei BE241753 Hs 74592 42 643 5280
422830 hypothetical protein DKFZp434P0111 AC007954 Hs 121371 42 1746 1747 6118
421937 hematological and neurological expresse AI878857 Hs 109706 42 1617 6024
427716 karyopheπn (importiπ) beta 1 L38951 Hs 180446 42 236323646556
402330 Target Exon 42 4678
412939 eukaryotic translation elongation facto AW411491 Hs 75069 42 657 5292
449436 hypothetical protein DKFZp434l2117 AA860329 Hs 279307 42 4087 7969
420582 Homo sapiens chromosome 19, cosmid R283 BE047878 Hs 99093 42 1464 5915
413313 glycyl-tRNA synthetase NMJ302047 Hs 293885 42 6997005325
406534 Target Exon 42 4809
422173 phorbolin-like protein MDS019 (CEM15) BE385828 Hs 250619 42 1656 6052
417037 antigen identified by monoclonal antibo BE083936 Hs 80976 42 1063 5608
418583 hypothetical protein AA604379 Hs 86211 42 1259 5758
418196 KIAA1708 protein A1745649 Hs 26549 42 1199 5716
429399 ESTs AA452244 Hs 16727 42 2556 6705
450172 signal transduction protein (SH3 contai NM 005864 Hs 24587 42 413941408014
446627 hypothetical protein SBBI48 AI973016 Hs 15725 42 3862 7783
418956 KIAA0788 protein AA234831 Hs 348493 42 1287 5778
438626 ESTs AI198059 Hs 26370 42 3342 7328
419335 hypothetical protein FLJ12888 AW960146 Hs 284137 42 1330 5813
444153 hypothetical protein FLJ10748 AK001610 Hs 10414 42 3680 3681 7638
421949 G8 protein N47378 Hs 109798 42 1620 6026
417410 PC4 and SFRS1 interacting protein 1 AF063020 Hs 82110 42 1114 11155651
438662 cleavage and polyadenylation specific f AA223599 Hs 6351 42 3345 7330
454390 KIAA0906 protein AB020713 Hs 56966 42 449744988304
430130 Homo sapiens mRNA, cDNA DKFZp761G02121 AL137311 Hs 23407442 26502651 6772
425966 cyclin F NM 001761 Hs 1 973 42 2158 21596409
430030 lectin, galactoside-bindmg, soluble, 1 BE300094 Hs 227751 42 2641 6764
436045 DKFZP564O0423 protein AB037723 Hs 5028 42 316931707176
429250 tryptophan rich basic protein H56585 Hs 198308 42 4541 6688
428099 ESTs AA421288 Hs 149025 42 2397 6583
408932 TP53TG3 protein AW594172 Hs 278513 42 277 5000
434371 KIAA1283 protein AA631362 Hs 120866 42 3050 7077
412723 hypothetical protein AF301222 AA648459 Hs 335951 42 634 5271
445162 piccolo (presynaptic cytomatnx protein AB011131 Hs 12376 42 3749 37507693
410211 zinc finger protein NM 014347 Hs 296365 42 431 4325114
420230 forkhead box C1 AL034344 Hs 284186 42 1434 14355893
458300 nbosomal protein L31 AW580932 Hs 164170 42 4572 8370
432618 hypothetical protein MGC2705 AA557284 Hs 172330 42 2893 6952
416224 reticulocalbm 2, EF-hand calcium bmdi NM 002902 Hs 7 9088 42 9839845550
421917 KIAA1020 protein AB028943 Hs 109445 42 1612 1613 6021
456759 delta (Drosophila) like 3 BE259150 Hs 127792 42 4528 8331
404420 C8001064* gι|6754928|ref|NP_035989 1 | o 42 4748
426981 KIAA0530 protein AL044675 Hs 173081 42 2292 6500 419900 ESTs AI469960 Hs 170698 42 1392 5860
420028 carbohydrate (N-acetylgIucosamιne-6-0) AB014680 Hs 8786 42 1408 14095872
408633 PRO2000 protein AW963372 Hs 222088 42 245 4975
440716 ESTs AW105245 Hs 307082 42 3485 7461
440491 ESTs, Weakly similar to 2109260A B cell R35252 Hs 130558 42 3468 7447
425848 valyl-tRNA synthetase 2 BE242709 Hs 159637 42 2150 6402
413097 ankyπn repeat-containing protein BE383876 Hs 75196 42 681 5312
424649 embryonic ectoderm development BE242035 Hs 151461 42 1983 6286
408621 chromosome 11 open reading frame 8 AI970672 Hs 46638 42 244 4974
445255 synaptosomal-associated protein, 91 kDa NMJJ14841 Hs 1 2477 42 375337547696
406648 major histocompatibility complex, class AA563730 Hs 277477 42 38 4817
424130 Homo sapiens mRNA, cDNA DKFZp586L141 (fAL050136 Hs 14094542 1903 6232
438253 hypothetical protein from EUROIMAGE 210 X65230 Hs 38004 42 3311 33127303
413010 transcription factor 6-lιke 1 (mitochon AA393273 Hs 75133 42 668 5301
430390 KIAA0969 protein AB023186 Hs 343666 42 2686 2687 6797
441495 ESTs AW294603 Hs 127039 42 3521 7494
452256 Homo sapiens cDNA FLJ10071 fis, clone H AK000933 Hs 28661 42 4306 8146
423198 cell division cycle 25A M81933 Hs 1634 42 1780 1781 6145
431393 ESTs, Highly similar to cytokine recept AW971493 Hs 134269 42 2780 6864
418283 cathepsm K (pycnodysostosis) S79895 Hs 83942 42 1210 1211 5724
447078 ESTs AW885727 Hs 9914 42 3888 7805
443698 hypothetical protein FLJ12529 AW961106 Hs 169100 42 3636 7599
436957 ESTs AA902488 Hs 122952 42 3228 7227
443898 Sec61 gamma AW804296 Hs9950 42 3655 7616
432265 SCG10-Iιke-proteιn BE382679 Hs 285753 41 2860 6924
400205 NM_006265* Homo sapiens RAD21 (S pombe Hs 81848 41 4598
414178 ESTs, Weakly similar to I38022 hypothet AW957372 Hs 46791 41 788 5396
435593 DKFZP586J1624 protein R88872 Hs 4964 41 3141 7153
402233 NM_030760* Homo sapiens endothelial dif 41 4674
409200 KIAA0076 gene product AL042914 Hs 51039 41 325 5037
408772 ESTs W88532 Hs 254562 41 256 4985
438930 hypothetical protein AL110115 AW843633 Hs 343261 41 3366 7349
441749 ESTs AW450805 Hs 199316 41 3536 7508
411395 KIAA1802 protein AA889673 Hs 7542 41 532 5190
441094 MYC-associated zinc finger protein (pur U33819 Hs 7647 41 349734987473
453896 KIAA1853 protein AW293483 Hs 255205 41 4461 8275
446073 hypothetical protein MGC5508 BE261001 Hs 13662 41 3818 7746
408056 ephrιn-A4 AA312329 Hs 42331 41 188 4930
430200 geminin BE613337 Hs 234896 41 2658 6777
408547 ESTs AA574291 Hs 57837 41 238 4969
408433 ras-related C3 botulmum toxin substrat AW162931 Hs 45002 41 221 4955
443837 spindle pole body protein AI984625 Hs 9884 41 3650 7612
436415 proliferation-associated 2G4, 38kD BE265254 Hs 343258 41 3186 7191
427087 uncharactenzed hypothalamus protein HT BE073913 Hs 173515 41 2301 6508
409596 KIAA0410 gene product BE244200 Hs 90421 41 364 5063
441955 ESTs AA972327 Hs 368431 41 3543 7515
445674 transcription factor CA150 BE410347 Hs 13063 41 3790 7722
412620 ESTs T58171 Hs 12253 41 617 5258
429617 B-cell CLUIymphoma7A X89984 Hs 211563 41 258925906728
441742 ESTs, Highly similar to A59266 unconven H21075 Hs 31802 41 3534 7506
414280 zyxm BE410769 Hs 75873 41 796 5403
423062 ESTs NM 003655 Hs 5637 41 1774 17756140
452092 hypothetical protein FLJ11210 BE245374 Hs 27842 41 4285 8128
413048 mannose receptor, C type 1 M93221 Hs 75182 41 6726735305
450785 Homo sapiens, alpha-1 (VI) collagen AA852713 Hs 108885 41 4193 8056
419594 topoisomerase (DNA) II binding protein AA013051 Hs 91417 41 1360 5834
450705 iroquois homeobox protein 2A (IRX-2A) U90304 Hs 25351 4 1 418541868050
411078 CocoaCπsp AI222020 Hs 182364 41 512 5172
419452 PTK7 protein tyrosine kinase 7 U33635 Hs 90572 41 13401341 5821
446215 SH3 domain binding glutamic acid-rich p AW821329 Hs 14368 41 3825 7753
449969 Homo sapiens cDNA FLJ14337 fis, clone P AW295142 Hs 180187 4 1 4123 8001
437762 synaptotagmin I T78028 Hs 154679 4 1 3284 7277
421931 gamma-aminobutyπc acid (GABA) A recept NMJ00814 Hs 1440 41 1615 16166023
411943 ESTs, Weakly similar to S44608 C02F56 BE502436 Hs 7962 41 562 5214
410160 ESTs AI124557 Hs 368306 41 427 5111
448072 ESTs AI459306 Hs 349096 4 1 3974 7876
418154 nuclear receptor subfamily 1 , group I, BE165866 Hs 352403 41 1197 5714
409869 GDP dissociation inhibitor 1 BE259015 Hs 74576 41 393 5085
444759 ESTs AW105011 Hs 371157 41 3721 7671
422599 non-metastatic cells 1, protein (NM23A) BE387202 Hs 118638 4 1 1710 6092
421753 ATP-biπding cassette, sub-family B (MDR BE314828 Hs 107911 41 1587 5999
405516 ENSP00000200457* Thyroid receptor inter 41 4785
454024 hypothetical protein FLJ23403 AA993527 Hs 293907 41 4481 8290
416959 ubiquitin-conjugat g enzyme E2A (RAD6 D28459 Hs 80612 41 1050 1051 5599
452187 transcription factor Dp-2 (E2F dimeπza AA400200 Hs 379018 41 4293 8135
449568 KIAA1598 protein AL157479 Hs 23740 41 4096 7977
453173 KIAA0442 protein AB007902 Hs 32168 41 43974398 8223
414702 cell division cycle 34 L22005 Hs 76932 41 8528535448
427857 hypothetical protein FLJ22865 AL133017 Hs 288679 41 2377 6566
423589 ESTs AA328082 Hs 361361 41 1822 6175
448186 Homo sapiens cDNA FLJ14208 fis, clone N AA262105 Hs 4094 41 3982 7883
426269 Homo sapiens mRNA, cDNA DKFZp566A1046 ( H15302 Hs 1689504 1 2190 6433
431192 ESTs, Weakly similar to SP62_HUMAN SPLl A1670056 Hs 137274 41 2759 6847
417164 heterogeneous nuclear πbonucleoprotein AA338283 Hs 81361 41 1087 5627
436639 fibroblast growth factor 9 (glia-activa D14838 Hs 111 41 320732087209
434775 ESTs AA648983 Hs 370514 41 3074 7098 448807 ESTs A1571940 Hs 7549 41 4041 7930 442990 hypothetical protein MGC11321 AA197226 Hs 19347 4 1 3592 7560 424756 lamin B receptor AW504657 Hs 152931 40 1997 6296 449458 ESTs AI805078 Hs 208261 40 4089 7971 438203 ESTs BE540090 Hs 7345 40 3308 7300 416737 LIM domain protein AF154335 Hs 79691 40 1028 1029 5582 447397 E-1 enzyme BE247676 Hs 18442 40 3923 7833 417871 ESTs AA521368 Hs 24252 40 1163 5686 452063 ESTs, Weakly similar to TWST_HUMAN TWIS R53185 Hs 32366 40 4281 8124 437967 mel transforming oncogene (derived from BE277414 Hs 5947 40 3294 7287 417259 chondroitin sulfate proteoglycan 2 (ver AW903838 Hs 81800 40 1092 5632 421057 Homo sapiens cDNA FLJ22063 fis, clone T58283 Hs 120638 40 1501 5940 416188 v-myc avian myelocytomatosis viral onco BE157260 Hs 79070 40 979 5546 448950 CGI-152 protein AF288687 Hs 9275 40 40504051 7936 418385 Homo sapiens, clone IMAGE 3357127, mRNA AW590613 Hs 30104040 1225 5734 431431 Human DNA sequence from clone RP3-403A1 AL096711 Hs 118744 40 2784 6868 423662 B-cell CLUIymphoma 11A (zinc finger pr AK001035 Hs 130881 40 1835 1836 6185 430287 ESTs, Weakly similar to LEU5J.UMAN LEUK AW182459 Hs 12575940 2676 6790 449281 hypothetical protein MGC15668 AI808699 Hs 162717 40 4078 7960 441551 ESTs AA318224 Hs 296141 40 3524 7497 438501 phosphomositol 3-phosphate binding pro Z44110 Hs 86149 40 3328 7318 443262 interleukin enhancer binding factor 3, AF167570 Hs 256583 40 361336147580 451999 DEAD/H (Asp-Glu-Ala Asp/His) box polype AW176401 Hs 380623 40 4268 8115 424441 H2A histone family, member X X14850 Hs 147097 40 195219536267 414493 retinoblastoma binding protein 2 AL133921 Hs 76272 40 826 5427 424720 SWI/SNF related, matrix associated, act M89907 Hs 152292 40 1990 1991 6292 422326 eukaryotic translation initiation facto AI114875 Hs 78592 40 1672 6064 448196 hypothetical protein FLJ10520 BE543313 Hs 77510 40 3983 7884 401153 Target Exon 40 4645 433180 K562 cell derived leucine-zipper-like p AB038651 Hs 31854 40 294929506997 435931 RNA binding motif protein 9 AI077464 Hs 351478 40 3163 7171 428677 troponin I, cardiac AI657119 Hs 351582 40 2462 6634 447898 62 kd protein AW969638 Hs 380920 40 3966 7868 419752 ESTs, Moderately similarto ZN91_HUMAN AA249573 Hs 152618 40 1386 5854 413254 isocitrate dehydrogenase 3 (NAD) gamma U40272 Hs 75253 40 691 6925320 439490 ESTs, Weakly similar to A46302 PTB-asso AW249197 Hs 100043 40 3401 7384 433808 ART-4 protein NM_014062 Hs 3566 40 300530067041 418327 paired like homeodomam transcription f U70370 Hs 84136 40 1217 1218 5729 416283 vascular endothelial growth factor C NM 005429 Hs79141 40 9859865551 432974 ESTs BE348793 Hs 233331 40 2919 6973 426423 stngle-stranded-DNA-biπdiπg protein NM 012446 Hs 1 69833 40 222222236455 435937 ESTs AA830893 Hs 119769 40 3164 7172 447082 thioredoxin-like T85314 Hs 54629 40 3889 7806 423896 ESTs AA332216 Hs 130584 40 1862 6204 424176 hypothetical protein AL137273 Hs 142307 40 1909 19106237 437464 Homo sapiens mRNA, cDNA DKFZp547J047 (f AA323296 Hs 97837 40 3266 7261 427472 transposon-denved Buster3 transposase- AA522539 Hs 131250 40 2333 6531 437546 T-box 1 AW074836 Hs 173984 40 3270 7264 414682 inhibitor of DNA binding 3, dominant ne AL021154 Hs 76884 40 8448455443 446566 membrane-spanning 4-domaιns, subfamily H95741 Hs 17914 40 3857 7778 413433 transcription factor 4 NM 003199 Hs 326198 40 7167175336 449349 hypothetical protein FLJ21939 similar t AI825386 Hs 381224 40 4083 7965 413408 DEAD/H (Asp-Glu-Ala-Asp/His) box polype R51793 Hs 1440 40 714 5334 413823 ESTs AI341417 Hs 29406 40 747 5362 409995 ESTs AW960597 Hs 129206 40 402 5093 435466 G protein beta subuπit-like BE619165 Hs 29203 40 3128 7144 409392 ESTs AA973020 Hs 59710 40 346 5050 435557 ESTs, Moderately similar to I54374 gene AA864704 Hs 67197 40 3138 7151 422436 KIAA0756 protein AB018299 Hs 13349 40 168216836071
TABLE 6B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
429163 1238297J AW974271 AA592975 AA447312 AA884766
411962 2307710 1 AA099050 AA099526 T47733
448044 1111791 1 A 867082 AI458682 H24240 R18426 R14537
417588 33114_3 R24958 Z44510 T82024 R00714
TABLE 6C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers 'Dunham l et al refers to the publication entitled
The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489 495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
402994 2996643 Minus 4727 4969
406367 9256126 Minus 58313-58489
401621 8570184 Minus 193 608
401797 6730720 Plus 6973-7118
403857 7708910 Minus 2524-3408 404208 3080468 Minus 105346-105573
404030 7671252 Plus 149362-151749
401827 2262095 Plus 94725-94860,98452-98660
405770 2735037 Plus 61057-62075
406311 9211559 Minus 137114-139033
405754 3688349 Plus 19448-19610,20242-20699
400991 8096825 Plus 159197-159320
402992 7767907 Minus 42137-42515
406137 9166422 Minus 30487-31058
405268 4156151 Minus 24404-24521
406076 9123123 Plus 89972-90319
403650 8705512 Plus 71272-71414
404632 9796668 Plus 45096 45229
405326 4375975 Plus 10633-10709,30805 30893,38078-38253,5511
402861 2814366 Minus 14933-15231,15387-15627
405387 6587915 Minus 3769-3833,5708-5895
403668 7259739 Plus 39942-40150
402260 3399665 Minus 113765-113910,115653-115765,116808-11694
402330 4464283 Minus 15325-15380,15484-15588,15842-15915
406534 7711477 Plus 40463-40586,41191-41336,41856-41986,4300
404420 7407952 Minus 129817-130586
402233 7690102 Plus 90281-91477
405516 9454624 Plus 112707-112876,113676 113854
401153 9438289 Plus 30582-30801
TABLE 7A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UmGeπe Unigene number
RATIO 95th percentile of soft tissue sarcoma AIs divided by the 50th percentile of normal tissue AIs, where thi subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
413778 myosin, light polypeptide 2, regulatory AA090235 Hs 75535 450 740 5356
428087 troponin C2, fast AA100573 Hs 182421 42 8 2396 6582
407245 titin X90568 Hs 172004 427 1321334881
425545 Homo sapiens, clone MGC 12401, mRNA, co N98529 Hs 158295 340 2114 6379
426752 titin X69490 Hs 172004 340 22662267 6482
409601 keratin 1 (epidermolytic hyperkeratosis AF237621 Hs 80828 32 2 3653665064
412519 troponin T1, skeletal, slow AA196241 Hs 73980 31 6 598 5244
406704 myosin, heavy polypeptide 7, cardiac mu M21665 Hs 929 298 65 564826
409169 (clone PWHLC2-24) myosin light chain 2 F00991 Hs 50889 293 316 5029
428221 ATPase, Ca transporting, cardiac muscle U96781 Hs 183075 280 240824096592
400440 nebulm X83957 Hs 83870 260 24254627
422633 enolase 3, (beta, muscle) X56832 Hs 118804 257 1716 17176098
407013 gb Human nebulm mRNA, partial eds U35637 Hs 83870 255 94954851
422867 cartilage oligomeric matrix protein (ps L32137 Hs 1584 25 1 1751 17526122
406706 myosin, heavy polypeptide 1, skeletal m X03740 Hs 231581 248 59604828
417070 titin Z19077 Hs 172004 246 1070 5614
424687 matrix metalloproteinase 9 (gelatmase i J05070 Hs 151738 236 1986 1987 6289
426300 delta like homolog (Drosophila) U15979 Hs 169228 223 219621976437
406707 myosin, heavy polypeptide 2, skeletal S73840 Hs 931 22 2 61 624829
412129 troponin T3, skeletal, fast M21984 Hs 73454 221 571 5725222
431204 cytochrome c oxidase subunit Via polype F28841 Hs 250760 21 4 2760 6848
422640 troponin C, slow M37984 Hs 118845 21 0 1718 17196099
421296 penlipin NM J02666 Hs 1 03253 20 3 1525 15265961
416931 adipose most abundant gene transcript 1 D45371 Hs 80485 199 1047 10485597
418205 troponin I, skeletal, fast L21715 Hs 83760 195 1204 1205 5720
405001 interleukin enhancer binding factor 1 194 4767
441134 cellular retinoic acid-binding protein W29092 Hs 346950 194 3500 7475
410621 titin AA194329 Hs 172004 193 481 5149
421773 ESTs W69233 Hs 112457 187 1588 6000
420139 lipase, hormone-sensitive NM..005357 Hs 95351 184 1419 14205881
417153 collagen, type II, alpha 1 (primary ost X57010 Hs 81343 179 1084 10855625
422069 titin cap (telethon ) AJ010063 Hs 343603 179 1635 1636 6037
417435 carbonic anhydrase III, muscle specific NMJ305181 Hs 82129 172 1121 1122 5655
427899 serum amyloid A1 AA829286 Hs 336462 17 1 2384 6571
452838 preferentially expressed antigen in mel U65011 Hs 30743 169 435743588188
410223 calsequestnn 1 (fast-twitch, skeletal S73775 Hs 60708 168 4334345115
408591 mammaglobiπ 1 AF015224 Hs 46452 166 241 2424972
446523 sarcolipm NM 003063 Hs 334629 164 385238537774
418533 myosin-bindmg protein C, fast type NM_004533 Hs 85937 163 1253 12545754
420197 ESTs, Weakly similar to A57291 cytokine AW139647 Hs 88134 16 1 1429 5889
416373 ESTs, Weakly similar to S12658 cysteine AA195845 Hs 73680 161 996 5559
404977 Insulin like growth factor 2 (somatomed 160 4766
424688 myosin light polypeptide 3, alkali, ve AA216287 Hs 1815 160 1988 6290
431205 tropomodulm 4 (muscle) AA194560 Hs 250763 158 2761 6849
418391 troponin I, skeletal, slow NM 003281 Hs 84673 155 1228 12295736
409096 sarcomeric muscle protein AA194412 Hs 50550 152 302 5019
403088 NMJ03319* Homo sapiens titin (TTN), mR 15 1 4707
424982 phosphorylase, glycogen, muscle (McArdl U94777 Hs 351580 15 1 2036 20376325
447205 ESTs, Moderately similar to T17372 p las BE617015 Hs 11006 149 3900 7816 418390 titin immunoglobulin domain protein (my AF133820 Hs 84665 148 1226 12275735 421566 early growth response 2 (Krox-20 (Droso NM_000399 Hs 1 395 147 1563 15645984 406964 FGENES predicted novel secreted protein M21305 145 87884847 429359 matrix metalloproteinase 14 (membrane i W00482 Hs 2399 145 2551 6702 419138 ryanodme receptor 1 (skeletal) U48508 Hs 89631 139 1309 1310 5796 431360 loπcπn NM_000427 Hs 251680 139 27762777 6861 419648 thyroid hormone responsive SPOT14 (rat) T73661 Hs 91877 138 1366 5839 427666 calmodulm-like skin protein (CLSP) AI791495 Hs 180142 137 2356 6550 431089 ESTs, Weakly similar to unknown protein BE041395 Hs 374629 137 2745 6838 426429 myosin-bmding protein C, slow-type X73114 Hs 169849 136 22242225 6456 439496 Homo sapiens, Similar to RIKEN cDNA 111 BE616501 Hs 32343 135 3402 7385 408493 phosphoglycerate mutase 2 (muscle) BE206854 Hs 46039 134 231 4962 420783 lectin, galactoside-binding, soluble, 7 AI659838 Hs 99923 133 1478 5924 400499 C10001858 gι|6679124|ref|NP_032759 1| n 133 4628 407102 glycerol-3 phosphate dehydrogenase 1 (s AA007629 Hs 348601 132 109 4861 422424 prostate differentiation factor Al 186431 Hs 296638 132 1681 6070 424399 AI905687 IL-BT095-190199-019 BT095 Homo AI905687 Hs 348419 129 1942 6259 417389 midkine (neuπte growth-promoting facto BE260964 Hs 82045 128 1109 5647 430411 bone gamma carboxyglutamate (gla) prole X51699 Hs 2558 127 2691 26926800 437206 ESTs, Weakly similar to I38344 Mm, c AW975934 Hs 172004 126 3245 7242 434352 small muscle protein, X-lmked AF129505 Hs 86492 126 30473048 7075 430681 ESTs AW969675 Hs 291232 125 2719 6819 453857 Ras-induced senescence 1 (RIS1) AL080235 Hs 35861 125 444944508266 445263 KIAA1560 protein H57646 Hs 42586 124 3755 7697 429973 ESTs AI423317 Hs 164680 124 2628 6756 406687 matrix metalloproteinase 11 (slromelysi M31126 Hs 352054 123 49504823 414152 thrombospondm 4 NMJ03248 Hs 75774 122 7827835391 446619 secreted phosphoprotein 1 (osteopontin AU076643 Hs 313 122 3861 7782 429997 apolipoprote B mRNA editing enzyme, c NMJJ06789 Hs 227457 122 26362637 6761 403593 Target Exon 12 1 4725 444381 hypothetical protein BC014245 BE387335 Hs 283713 12 1 36977652 419050 adenosine monophosphate deammase 1 (is NM_000036 Hs 89570 12 1 129312945784 416378 ankyπn repeat domain 2 (stretch respon AW044467 Hs 73708 12 1 9975560 427809 lipoproteiπ lipase M26380 Hs 180878 120 23736562 450701 hypothetical protein XP 98151 (leucine H39960 Hs 288467 11 7 41838048 408915 heptacellular carcinoma novel gene-3 pr NM_016651 Hs 48950 11 6 2742754998 453331 ESTs AI240665 Hs 352537 11 6 44138236 436519 myozenin AJ278124 Hs 238756 11 5 319631977200 418072 Human DNA sequence from clone RP3-353C1 F35210 Hs 86507 11 5 11905707 443727 ESTs Z25389 Hs 18459 11 4 36407603 417866 collagen, type XI, alpha 1 AW067903 Hs 82772 11 3 11625685 446921 small inducible cytokine subfamily A (C AB012113 Hs 16530 11 3 387838797797 408536 ESTs AW381532 Hs 135188 11 1 2364967 411102 tπadin AA401295 Hs 23926 11 1 5155175 416349 myomesin (M-protein) 2 (165kD) X69089 Hs 79227 11 1 9919925556 418399 hypothetical protein FLJ12442 AF131781 Hs 84753 109 123212335738 444329 hypothetical protein FLJ12921 W73753 Hs 209637 108 36937648 443514 ESTs BE464288 Hs 25475 108 36247588 416559 ESTs AI039195 Hs 128060 108 10125571 419875 proenkephalin AA853410 Hs 93557 107 13915859 429259 Plakophilm AA420450 Hs 380088 107 25356689 417308 KIAA0101 gene product H60720 Hs 81892 107 10945634 409944 four and a half LIM domains 3 BE297925 Hs 57687 107 3995090 400651 ENSP00000228031* COPPER CHAPERONE FOR S 107 4636 428769 ESTs A AWW220077117755 Hs 106771 106 24706640 418678 cancer/testis antigen (NY-ESO-1) NNMM 00001133227 Hs 87225 105 126912705765 450787 aquapoππ 7 AABB000066119900 Hs 25475 104 419441958057 418054 lysyl oxidase-like 2 NNMMJJ002233I18 Hs 83354 104 118411855702 401781 Target Exon 104 4662 428405 cholinergic receptor, nicotmic, alpha Y Y0000776622 Hs 2266 103 243624376615 409178 kallikrein 5 BBEE339933994488 Hs 50915 103 3195032 410687 lysyl oxidase-like 1 UU2244338899 Hs 65436 102 4854865153 425292 37 kDa leucine πch repeat (LRR) protei NNMMJ 0005588224 Hs 1 55545 102 208320846359 413011 biglycan AAWW006688111155 Hs 821 101 6695302 427335 G antigen 7B AAAA444488554422 Hs 278444 101 23176520 422887 ESTs AAII775511884488 Hs 49215 10 1 17556124 432874 melanoma inhibitory activity WW9944332222 Hs 279651 100 29136968 419741 ubiquitm carrier protein E2-C NNMM 0J00770011!9 Hs 93002 100 137913805850 418004 aldehyde dehydrogenase 3 family, member U37519 Hs 87539 99 117411755695 419301 tenomodulm protein AA236166 Hs 132957 99 13285811 442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 99 35517523 422060 ESTs, Moderately similar to ALU5_HUMAN R20893 Hs 325823 99 16336035 437330 Homo sapiens mRNA, cDNA DKFZp761 J1112 ( AL353944 Hs 50115 99 32537250 417515 ataxia-telangiectasia group D associate L24203 Hs 82237 9 9 112911305659 408202 DKFZP586L151 protein AA227710 Hs 43658 99 2024942 428471 stratifin X57348 Hs 184510 99 244524466622 411021 titin F00055 Hs 172004 98 5085169 428848 leptm (murine obesity homolog) NMJ00230 Hs 1 94236 98 248124826649 421512 myomegalin AB007923 Hs 265848 98 155415555979 456115 F01082 Hs 172004 45158320 446962 muscle specific ring finger protein 1 AI351421 Hs 279709 97 38847801 417405 ESTs W28657 Hs 5307 97 11125649 426600 VGF nerve growth factor inducible NMJ03378 Hs 1 71014 96 225522566475 450375 a disintegnn and metalloproteinase dom AA009647 Hs 352537 96 41598028 420067 Homo sapiens mRNA, cDNA DKFZp5640222 (f T52431 Hs 94795 96 14145876 421823 ESTs N40850 Hs 28625 96 16006011 431211 gap junction protein, beta 2, 26kD (con M86849 Hs 323733 96 27622763 6850
431830 small inducible cytokine subfamily A (C Y16645 Hs 271387 94 282728286900
423961 peπostin (OSF-2os) D13666 Hs 136348 94 1878 18796215
409028 Z band alternatively spliced PDZ-motif AB014513 Hs 49998 94 296 2975015
421552 secreted frizzled related protein 4 AF026692 Hs 105700 94 1559 15605982
429892 myomesin 1 (skelemin) (185kD) NM_003803 Hs 2504 94 261426156745
429500 hexabrachioπ (tenascm C, cytotactin) X78565 Hs 289114 94 257425756718
416982 creatine kinase, mitochondnal 2 (sarco J05401 Hs 80691 93 1055 10565602
418156 nuclear receptor subfamily 1, group 1, W17056 Hs 83623 93 1198 5715
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 93 3057 7083
435370 ESTs AI964074 Hs 225838 92 3120 7136
420208 silver (mouse homolog) like BE276055 Hs 95972 92 1431 5891
422871 collagen, type XI, alpha 2 AL031228 Hs 121509 92 1753 17546123
401780 NM_005557* Homo sapiens keratin 16 (foe 9 1 4661
438089 nuclear receptor subfamily 1, group I, W05391 Hs 351546 91 3301 7294
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 90 1669 16706062
429134 ESTs AA446953 Hs 99004 90 2514 6673
445234 ESTs AW137636 Hs 146059 90 3751 7694
427639 Homo sapiens, clone MGC 18257, mRNA, co AW444530 Hs 350860 90 2353 6547
428748 Ksp37 protein AW593206 Hs 98785 89 2468 6638
412560 CCR4-NOT transcription complex, subunit R24601 Hs 350495 89 602 5248
418140 microfibπllar-associated protein 2 BE613836 Hs 83551 89 1196 5713
428698 KIAA1866 protein AA852773 Hs 334838 89 2463 6635
411789 Adlican AF245505 Hs 72157 89 5535545207
434326 reticulon 2 NM J05619 Hs 3803 89 304330447073
420798 keratin 10 (epidermolytic hyperkeratosi W93774 Hs 99936 89 1479 5925
430713 eukaryotic translation elongation facto AA351647 Hs 2642 88 2726 6824
451681 ESTs Weakly similarto AA64_HUMAN 64 K Z28564 Hs 255950 88 4245 8097
424408 collagen, type V, alpha 1 AI754813 Hs 146428 88 1943 6260
428305 cartilage linking protein 1 AA446628 Hs 2799 87 2426 6607
414482 endothelm receptor type A S57498 Hs 76252 87 8248255426
428957 ' WNT1 inducible signaling pathway protei NM W3881 Hs 1 94679 87 2491 24926656
412472 ESTs AW975398 Hs 293836 87 593 5240
410001 kallikrein 11 AB041036 Hs 57771 87 4034045094
428398 ESTs AI249368 Hs 98558 87 2435 6614
418113 SRY (sex determining region Y)-box 4 AI272141 Hs 83484 87 1194 5711
428289 complement component 2 M26301 Hs 2253 87 2421 24226603
411296 growth suppressor 1 BE207307 Hs 10114 87 524 5183
438091 nuclear receptor subfamily 1, group I, AW373062 Hs 351546 86 3302 7295
436555 ESTs, Weakly similar to 2003319A ankyπ AI972007 Hs 304646 86 3200 7202
410079 glycogenin 2 U94362 Hs 380757 86 4184195104
419550 KIAA0128 protein, septin 2 D50918 Hs 90998 86 1348 13495827
452023 KIAA1173 protein AB032999 Hs 27566 86 4271 42728118
415989 ESTs AI267700 Hs 351201 86 962 5530
424086 lysyl oxidase AI351010 Hs 102267 85 1896 6227
422511 collagen, type XVII, alpha 1 AU076442 Hs 117938 85 1692 6078
412326 small inducible cytokine A3 (homologous R07566 Hs 3817 85 582 5231
416783 monocyte to macrophage differeπtiation- AA206186 Hs 79889 85 1031 5584
413554 secretogranm II (chromogranin C) AA319146 Hs 75426 85 729 5346
407112 ESTs, Weakly similar to ALU7_HUMAN ALU AA070801 Hs 51615 85 111 4863
418064 S100 calcium-binding protein, beta (neu BE387287 Hs 83384 85 1188 5705
406673 major histocompatibility complex, class M34996 Hs 198253 85 9091 4821
416658 fibπllin 2 (congenital contractural ar U03272 Hs 79432 85 1020 1021 5577
435101 ESTs A1743156 Hs 131064 85 3106 7124
424800 MyoD family inhibitor AL035588 Hs 153203 84 200220036300
420103 aldehyde dehydrogenase 1 family, member AA382259 Hs 95197 84 1416 5878
414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 83 789 5397
420813 prolactiπ induced protein X51501 Hs 99949 83 1482 14835927
423044 protocadhenn 18 AA320829 Hs 97266 83 1772 6138
418026 fatty acid binding protein 4, adipocyte BE379727 Hs 83213 83 1179 5698
433430 ESTs AI863735 Hs 369982 83 2977 7018
409633 ESTs AW449822 Hs 55200 83 371 5068
443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 83 3621 36227586
445537 EGF-like-domaiπ, multiple 6 AJ245671 Hs 12844 82 37803781 7716
411852 ESTs, Weakly similar to T00329 hypothet AA528140 Hs 107515 82 655 5208
445016 reelm U79716 Hs 12246 82 373837397684
415672 ESTs N53097 Hs 193579 82 937 5511
408349 homeo box C10 BE546947 Hs 44276 8 1 213 4949
456063 retinol-bindmg protein 4, interstitial NM 006744 Hs 76461 8 1 4511 45128317
422087 matrix metalloproteinase 2 (gelatmase X58968 Hs 111301 8 1 1641 6040
423778 flavin containing monooxygenase 2 Y09267 Hs 132821 81 1846 18476193
413902 CD36 antigen (collagen type I receptor, AU076743 Hs 75613 81 752 5366
449722 cyclin B1 BE280074 Hs 23960 8 1 4112 7990
423024 ESTs, Moderately similar to ALU5.HUMAN AA593731 Hs 325823 8 1 1770 6136
449048 similar to S68401 (cattle) glucose du Z45051 Hs 22920 81 4061 7945
421690 calbindm 2, (29kD, calret in) AW162667 Hs 106857 80 1580 5994
409103 XAGE-1 protein AF251237 Hs 112208 80 304305 5021
426991 Homo sapiens cDNA FLJ10674 fis, clone N AK001536 Hs 214410 80 2294 6502
457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 80 4561 8359
450300 ESTs, Highly similar to ITH4JHUMAN INTE AL041440 Hs 58210 80 4154 8024
452862 ADAMTS2 (a disintegnn like and etall AW378065 Hs 8687 80 4360 8190
403071 NM 003319* Homo sapiens tιtιn (TTN), R 80 4702
412719 ESTs AW016610 Hs 816 80 633 5270
447377 transcription factor AP-2 alpha X77343 Hs 334334 79 39203921 7831
430686 desmoglein 1 NMJ01942 Hs 2633 79 2721 27226821
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 79 209921006369 452620 ESTs AA436504 Hs 119286 79 4338 8172 423575 intron of peπoεbn (OSF-2os) C18863 Hs 163443 79 1820 6173 453817 ESTs AW755253 Hs 379636 79 4442 8260 442082 calsyntenιn-2 R41823 Hs 7413 78 3550 7522 442376 HomosapienscDNAFLJ12228fis,clone MW95588 Hs 129982 78 3557 7529 423739 ESTs AA398155 Hs 97600 78 1842 6190 440042 ESTs AI073387 Hs 133898 78 3448 7430 435523 membrane-spanning 4-domaιns, subfamily T62849 Hs 11090 78 3131 7147 431048 cell death inducing DFFA-like effector R50253 Hs 249129 78 2742 6835 409632 serine (or cysteine) proteinase inhibit W74001 Hs 55279 78 370 5067 417689 KIAA0128 protein, septin 2 AA828347 Hs 90998 78 1148 5673 422148 histidine-nch calcium-binding protein M60052 Hs 1480 77 1651 1652 6048 433447 neuronal pentraxin II U29195 Hs 3281 77 2980 2981 7021 423201 growth hormone receptor NM_000163 Hs 1 25180 77 1782 17836146 443071 complement component 1 , q subcomponent, AL080021 Hs 8986 77 3598 7566 425071 deiodmase, lodothyronme, type NM_013989 Hs 1 54424 77 204320446330 419407 hypothetical protein FLJ21276 AW410377 Hs 41502 77 1334 5817 420212 calcium channel, voltage dependent, L t NM 000069 Hs 1 294 76 1432 1433 5892 439688 hypothetical protein FLJ12921 AW445181 Hs 209637 76 3418 7401 445033 cyclin dependent kinase inhibitor 2B (p AV652402 Hs 72901 76 3740 7685 454140 hypothetical protein FLJ 10474 AB040888 Hs 41793 76 449344948301 414443 platelet deπved growth factor receptor AU077268 75 817 5421 415702 gb HSPD18414 HM3 Homo sapiens cDNA clon F28877 Hs 73680 75 942 5515 421335 ARS component B X99977 Hs 103505 75 1529 15305964 417333 bromodomam and PHD finger containing, AL157545 Hs 173179 75 1096 5636 439755 B7 homolog 3 AW748482 Hs 77873 75 3430 7413 407604 collagen, type VIII, alpha 2 AW191962 Hs 353001 75 145 4891 412140 RAB6 interacting, k esin-like (rabkine AA219691 Hs 73625 75 573 5223 412473 ESTs F23393 Hs 153060 75 594 5241 414386 haptoglobm X00442 Hs 75990 75 810811 5415 424734 ESTs A1217685 Hs 96844 75 1992 6293 409327 collagen, type IX, alpha 3 L41162 Hs 53563 75 341 3425047 413566 sprouty (Drosophila) homolog 4 AW604451 Hs 381153 75 730 5347 420202 putative lymphocyte G0/G1 switch gene AL036557 Hs 95910 75 1430 5890 414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 75 8768775465 418045 ESTs AI972919 Hs 118837 75 1183 5701 417849 nidogen 2 AW291587 Hs 82733 74 1161 5684 444301 aspoπn (LRR class 1) AK000136 Hs 10760 74 3691 36927647 422627 transforming growth factor, beta induce BE336857 Hs 118787 74 1715 6097 406664 glycerol 3 phosphate dehydrogenase 1 (s L34041 Hs 348601 74 83844819 417900 CDC20 (cell division cycle 20, S cerev BE250127 Hs 82906 74 1165 5688 415655 ESTs W05433 Hs 352293 74 932 5506 403081 NM_003319* Homo sapiens titin (TTN), mR 74 4704 417045 Homo sapiens ORF1 F01180 Hs 332030 74 10665610 414002 FBJ murine osteosarcoma viral oncogene NM_006732 Hs 75678 74 7637645375 413132 protein kinase (cAMP-dependent, catalyt NM_006823 Hs 5209 73 6836845314 453392 SRY (sex determining region Y)-box 11 U23752 Hs 32964 73 441644178239 438746 Human melanoma associated antigen p97 ( AI885815 Hs 184727 73 33537337 407228 hemoglobin, beta M25079 Hs 155376 73 1241254876 409142 SMC4 (structural maintenance of chromos AL136877 Hs 50758 73 3123135027 421458 carbohydrate (keratan sulfate Gal 6) su NM_003654 Hs 1 04576 73 154315445972 411000 ESTs, Weakly similar to S38383 SEB4B pr N40449 Hs 201619 73 5055167 425234 ESTs, Weakly similar to I38022 hypothet AW152225 Hs 165909 73 20706349 422168 S100 calcium binding protein A7 (psona AA586894 Hs 112408 73 16546050 433122 ESTs AB019391 Hs 58049 73 2941 6991 414085 aldehyde dehydrogenase 1 family, member AA114016 Hs 75746 73 7755384 420376 protocadhenn 18 AL137471 Hs 97266 73 144714485903 443021 lg superfamily protein AA368546 Hs 8904 73 35937561 400295 AI905687 IL-BT095-190199 019 BT095 Homo W72838 Hs 348419 73 64617 457411 iroquois class homeobox protein IRX2 AW085961 Hs 130093 73 45498349 439285 hypothetical protein FLJ20093 AL133916 Hs 47860 73 33897372 428981 ESTs, Weakly similar to ALU2J.UMAN ALU BE313077 Hs 93135 72 24976660 421155 lysyl oxidase H87879 Hs 102267 72 15125950 431553 cartilage linking protein 1 X78075 Hs 2799 72 27926874 414175 hypothetical protein DKFZp761D112 AI308876 Hs 103849 72 7865394 421143 immunoglobulin superfamily containing I AB024536 Hs 102171 72 151015115949 407619 collagen, type IX, alpha 2 AL050341 Hs 37165 72 1461474892 412978 homeo box C6 A1431708 Hs 820 72 6655298 428824 ESTs W23624 Hs 173059 72 24776645 422048 spondin 2, extracellular matrix protein NMJ512445 Hs 288126 72 163116326034 407788 SlOO calcium-b ding protein A2 BE514982 Hs 38991 72 1614905 447499 protocadhenn beta 16 AW262580 Hs 147674 72 39347842 417376 LIM protein (similar to rat protein km AA253314 Hs 154103 72 11075645 459702 gb an03c03 x1 Stratagene schizo brain S AI204995 72 45968393 407172 gb ya92c05 si Stratagene placenta (9372 T54095 Hs 379019 72 1174869 452701 glutamine fructose 6 phosphate transami NM_005110 Hs 30332 71 434543468178 426509 pentaxm-related gene rapidly induced M31166 Hs 2050 71 224322446468 401203 Target Exon 71 4647 438549 trmucleotide repeat containing 3 BE386801 Hs 21858 7 1 33317320 437898 ESTs W81260 Hs 43410 71 32937286 408988 Homo sapiens clone TUA8 Cn du chat reg AL119844 Hs 49476 7 1 2895009 430699 ESTs, Weakly similar to RET2_HUMAN RETI AW969847 Hs 292718 1 27236822 452683 progesterone membrane binding protein AI089575 Hs 374574 7 1 43418175 425682 nbosomal protein L3 like NM_005061 Hs 1 59191 7 1 212221236385 409361 sine oculis homeobox (Drosophila) homol NM J05982 Hs 54416 7 1 3443455049 439979 hypothetical protein FLJ10430 AW600291 Hs 6823 7 1 34427424 432191 hypothetical protein, clone Telethon(lt AA043193 Hs 273186 70 28516916 450098 hypothetical protein FLJ21080 W27249 Hs 8109 70 41348009 419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 70 138113825851 433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 70 292329246977 437395 hypothetical protein D FZp762M136 AL365408 Hs 351747 70 325832597254 449969 Homo sapiens cDNA FLJ14337 fis, clone P AW295142 Hs 180187 70 41238001 450447 hypothetical protein P15-2 AF212223 Hs 25010 70 416841698036 412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 70 5695220 425154 collagen, type IX, alpha 1 NMJ01851 Hs 1 54850 70 205520566339 421579 stem cell growth factor, lymphocyte sec NM_002975 Hs 1 05927 70 156715685987 414359 cadhenn 11, type 2, OB-cadhenn (osteo M62194 Hs 75929 70 8085413 418532 neurotrophic tyrosine kinase, receptor, F00797 Hs 374321 70 12525753 445417 a dismtegπn-like and metalloprotease AK001058 Hs 12680 69 37667705 412577 CD163 antigen Z22968 Hs 74076 69 6086095252 432239 matrix metalloproteinase 13 (collagenas X81334 Hs 2936 69 285628576921 409007 Homo sapιens mRNA, cDNA DKFZp434G0827 (AL122107 Hs 49599 6 9 2925012 452392 corneodesmosin L20815 Hs 507 69 432343248160 437275 ESTs, Weakly similar to A47582 B-cell g AW976035 Hs 292396 69 32517248 414831 protein kinase, cAMP-dependeπt, regulat M31158 Hs 77439 69 8788795466 419631 popeye protein 3 AW188117 Hs 356642 69 13655838 447033 Predicted gene Eos cloned, secreted w/ AI357412 Hs 157601 69 38857802 416431 titm AW384459 Hs 172004 69 10035565 426369 Kreisler (mouse) maf-related leucine zi AF134157 Hs 169487 69 221322146448 417074 guamdinoacetate N methyltransferase Z49878 Hs 81131 69 107110725615 426310 neurapeptide Y receptor Y1 NM_000909 Hs 1 69266 69 219922006439 439751 Homo sapiens mRNA full length insert oD AA196090 Hs 50794 69 34287411 429441 lipophilm B (uteroglobm family member AJ224172 Hs 204096 69 256025616706 437191 serine protease inhibitor, Kazal type, NMJ06846 Hs 331555 69 324132427239 417079 interleukin 1 receptor antagonist U65590 Hs 81134 69 107310745616 400419 Target AF084545 68 22234626 414812 moπokine induced by gamma interferon X72755 Hs 77367 8748755464 415657 ESTs F32261 Hs 133004 68 9345508 409041 Hypothetical protein, XP-051860 (KIAA11 AB033025 Hs 50081 68 2993005017 427747 seπne/threonine kinase 12 AW411425 Hs 180655 68 23656557 442432 hypothetical protein FLJ23468 BE093589 Hs 38178 68 35637535 453659 myogemc factor 6 (herculin) NM_002469 Hs 35937 68 445144528267 407711 KIAA1808 protein A1085846 Hs 25522 1514896 450506 fibroblast activation protein, alpha NMJJ04460 Hs 4 18 68 417041718037 421307 Homo sapiens mRNA, cDNA DKFZp434B0425 ( BE539976 Hs 10330568 15285963 433235 contactm 3 (plasmacytoma associated) AB040929 Hs 35089 68 296329647006 452401 tumor necrosis factor, alpha induced pr NM_007115 Hs 29352 68 432543268161 449238 muscle specific RING finger protein 3 AA428229 Hs 331561 68 40757957 449717 cerebral cell adhesion molecule AB040935 Hs 23954 68 411041117989 428722 tissue inhibitor of metalloproteinase 4 U76456 Hs 190787 68 246424656636 418506 Unknown protein for MGC 29643 (formerly AA084248 Hs 372651 68 12475748 451497 Wnt inhibitory factor-1 H83294 Hs 284122 68 42358089 410929 ESTs H47233 Hs 30643 68 5045166 418728 ESTs AW970937 Hs 293843 12715766 451917 Homo sapiens unknown mRNA AW391351 Hs 50820 68 4261 8108 450390 Human DNA sequence from clone RP11-234G N93227 Hs 348805 68 41638031 452363 Homo sapiens, Similar to complement com AI582743 Hs 94953 67 43228159 448719 tπnucleotide repeat containing 3 AA033627 Hs 21858 67 40287920 408486 sodium channel, voltage gated, type IV, L04236 Hs 46038 67 2282294960 412755 ESTs, Weakly similar to P4HAJHUMAN PROL BE144306 Hs 179891 67 6375274 417944 collagen, type V, alpha 2 AU077196 Hs 82985 67 11725693 422386 heparaπ sulfate (glucosamine) 3 O sulfo AF105374 Hs 115830 67 167616776067 415656 ESTs W84346 Hs 84673 67 9335507 424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs 93135 67 19076235 403087 NM..003319* Homo sapiens Win (TTN), mR 67 4706 424420 prostaglandm E synthase BE614743 Hs 146688 67 19496264 408204 protein tyrosine phosphatase type IVA, AA454501 Hs 43666 67 2034943 407792 putative secreted ligand homologous to AI077715 Hs 39384 67 1624906 425247 matπx metalloproteinase 11 (stromelysi NMJ105940 Hs 1 55324 67 207220736351 406837 immunoglobulin kappa constant R70292 Hs 156110 67 694836 448520 doublecortιn an CaM kιnase-lιke 1 AB002367 Hs 21355 67 401040117907 short stature homeobox 2 AF022654 Hs 55967 67 3783795074
433839 ESTs, Weakly similar to ALU1 HUMAN ALU F35430 Hs 146070 67 30087043 437220 GS1999full AL117542 Hs 334305 67 32477244 414716 Kv channel-interacting protein 2 AF199598 Hs 97044 66 8568575451 422667 ESTs H25642 Hs 132821 66 17236102 433138 semaphoπn sem2 AB029496 Hs 59729 66 294429456994 407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 66 1664910 442573 branched chain amιπotransferase 1, cyto H93366 Hs 7567 66 35707541 411396 ESTs C04646 Hs 85428 66 5335191 406519 C10001858 gι|6679124|ref|NP_032759 1| n 66 4808 410361 guanylate binding protein 1 , interferon BE391804 Hs 62661 66 4565132 446051 ephnπ-A3 BE048061 Hs 37054 66 38167744 452223 hypothetical protein MGC2827 AA425467 Hs 8035 66 43028142 429609 cell adhesion molecule with homology to AF002246 Hs 210863 66 258425856725 431183 KDEL (Lys Asp-Glu Leu) endoplasmic reti NM_006855 Hs 250696 66 275627576845 418478 cyclin dependent kinase inhibitor 2A (m U38945 Hs 1174 66 124512465747 417366 small proline rich protein 1 B (cornifin BE185289 Hs 1076 66 11045642 420981 peroxisome proliferative activated rece L40904 Hs 100724 66 149514965936 432131 muscle disease related protein AB033021 Hs 272564 66 284328446911 444371 forkhead box M1 BE540274 Hs 239 65 36967651 421508 absentin melanoma 2 L004833 Hs 105115 65 155115525977 409012 DKFZP434I216 protein AL117435 Hs 49725 65 2932945013 417027 tπadin AA192306 Hs 23926 65 1062 5607 426363 transforming growth factor, beta 3 M58524 Hs 2025 65 22102211 6446 451766 ephrιn-B3 NMJ01406 Hs 26988 65 425542568104 402621 Target Exon 65 4684 410270 tumor endothelial marker 1 precursor AF279142 Hs 195727 65 4424435121 453041 Homo sapiens cDNA FLJ11918 fis, clone H AI680737 Hs 289068 65 4384 8211 452063 ESTs, Weakly similar to TWST_HUMAN TWIS R53185 Hs 32366 65 4281 8124 425308 receptor tyrosine kiπase-like orphan re M97639 Hs 155585 65 208720886362 438915 Williams-Beuren syndrome chromosome reg AA280174 Hs 355711 65 3365 7348 414315 gb HSB65D052 STRATAGENE Human skeletal Z24878 65 803 5409 419833 Homo sapiens tryptophanyl-tRNA syntheta AA251131 Hs 220697 65 1388 5856 406646 major histocompatibility complex, class M33600 Hs 375570 65 36374816 446142 ESTs AI754693 Hs 145968 65 3820 7748 410611 KIAA1628 protein AW954134 Hs 20924 65 480 5148 431103 pleiotrophin (hepann binding growth fa M57399 Hs 44 65 274827496840 441636 Homo sapiens mRNA, cDNA DKFZp566E183 (f AA081846 Hs 7921 65 3530 7502 409731 thymosm, beta, identified in neuroblas AA125985 Hs 56145 64 386 5080 443184 ESTs AI638728 Hs 135159 64 3607 7574 456508 ESTs, Weakly similar to AF208855 1 BM-0 AA502764 Hs 123469 64 4521 8325 423563 protein kinase (cAMP-dependent, catalyt R34734 Hs 75209 64 1817 6171 416391 mesoderm specific transcnpt (mouse) ho A1878927 Hs 79284 64 999 5562 440650 Human DNA sequence from PAC 75N13 on ch R44692 Hs 326801 64 3477 7455 407826 calpain 3, (p94) AA128423 Hs 40300 64 167 4911 424634 cartilage intermediate layer protein, n NMJ03613 Hs 1 51407 64 1981 19826285 432408 ESTs, Weakly similar to A46010 X linked N39127 Hs 356235 64 2872 6934 436608 down syndrome critical region protein D AA628980 Hs 192371 64 3205 7207 429415 pracollagen C endopeptidase enhancer NM_002593 Hs 202097 64 2557 25586706 429294 Homo sapiens cDNA FLJ22463 fis, clone AA095971 Hs 198793 64 2540 6693 406387 Target Exon 64 4805 427337 Fc fragment of IgG, low affinity lllb, Z46223 Hs 176663 64 231823196521 431866 angiopoietin like 2 NM_012098 Hs 8025 64 283028316902 418059 gb zn56d05 s1 Stratagene muscle 937209 AA211586 64 11865703 421778 actin related protein 2/3 complex, subu AA428000 Hs 283072 64 1591 6003 432731 fibronectin 1 R31178 Hs 287820 64 29046961 448390 hypothetical protein AL035414 Hs 21068 64 39997897 434149 hypothetical protein MGC5469 Z43829 Hs 244624 64 30307063 431457 integπn, alpha 11 NMJJ12211 Hs 256297 64 278727886870 444006 type I transmembrane protein Fn14 BE395085 Hs 334762 63 36687627 447414 neuroblastoma (nerve tissue) protein D82343 Hs 74376 63 392439257834 410234 fructose-1,6 bisphosphatase 2 NMJ03837 Hs 6 1255 63 4354365116 418986 ESTs AI123555 Hs 293821 63 12885779 418883 acid phosphatase 5, tartrate resistant BE387036 Hs 1211 63 1281 5774 451934 ESTs AI540842 Hs 61082 63 42628109 429451 heme oxygenase (decycling) 1 BE409861 Hs 202833 63 25626709 422106 Fc fragment of IgG binding protein D84239 Hs 111732 63 164616476044 420576 KIAA1858 protein AA297634 Hs 54925 63 14635914 435793 KIAA1313 protein AB037734 Hs 4993 63 315231537162 409882 heat shock 27kD protein family, member AJ243191 Hs 56874 63 3953965087 445107 ESTs, Weakly similar to I38022 hypothet AI208121 Hs 147313 63 37447689 417675 similar to murine leucine nch repeat p AI808607 Hs 3781 63 11445670 435406 calcium/calmodulm dependent protein ki F26698 Hs 4884 63 31247140 415885 KIAA0161 gene product D79983 Hs 78894 63 9539545524 406925 glycerol-3 phosphate dehydrogenase 1 (s L34041 Hs 348601 63 83844845 433577 ESTs AW007080 Hs 284192 63 29897028 422746 glypican 3 NMJ04484 Hs 1 19651 63 173217336109 453575 peptidyl arginine deiminase, type II AB023211 Hs 33455 63 442544268246 448030 membrane-spanning 4-domaιns, subfamily N30714 Hs 325960 63 3971 7873 426935 collagen, type I, alpha 1 NMJ00088 Hs 1 72928 63 228822896498 430643 MEGF10 protein AW970065 Hs 287425 63 27176817 408562 roundabout (axon guidance receptor, Dro AI436323 Hs 31141 63 2404971 420005 ESTs AW271106 Hs 133294 63 14075871 429930 ESTs AI580809 Hs 352364 63 26236751 451811 hypothetical protein MGC1136 AA663485 Hs 8719 63 42598106 453514 ESTs AA036675 Hs 50918 63 44248245 416208 ESTs, Weakly similar to MUC2JHUMAN MUCI AW291168 Hs 41295 6 2 9815548 441188 ESTs AW292830 Hs 255609 62 35037478 440274 scrapie responsive protein 1 R24595 Hs 7122 62 34647443 410889 twist (Drosophila) homolog (acrocephalo X91662 Hs 66744 6 2 5015025164 447733 MAD2 (mitotic arrest deficient, yeast, AF157482 Hs 19400 62 395539567860 419290 spinal cord derived growth factor-B Al 128114 Hs 112885 6 2 13275810 408212 hypothetical protein AA297567 Hs 43728 62 2064945 424481 proteolipid protein 1 (Pelizaeus-Merzba R19453 Hs 1787 62 19606272 434096 pleiomorphic adenoma gene-like 1 AW662958 Hs 75825 6 2 30297062 413031 phosphofructokinase, muscle BE515051 Hs 75160 6 2 6715304 453880 ESTs, Weakly similar to I38022 hypothet AI803166 Hs 135121 62 44588272 424870 ESTs T15545 Hs 244624 62 20146308 418203 CDC28 protein kinase 2 X54942 Hs 83758 6 2 120212035719 457211 ESTs Weakly similar to S51797 vasodila AW972565 Hs 32399 62 45438344 417068 hypothetical protein MGC3169 AA451910 Hs 85852 62 10695613 412471 endothelial cell growth factor 1 (plate M63193 Hs 73946 6 2 5915925239 436252 Homo sapiens cDNA FLJ 11562 fis, clone H AI539519 Hs 142827 62 31797184 443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 6 2 36567617 424455 calcium channel, voltage dependent, gam AA452006 Hs 147989 6 2 19576270 414555 phospholipase A2, group )IA (platelets, N98569 Hs 76422 62 8305431 429299 hypothetical protein MGC13102 AI620463 Hs 347408 62 25416694 410102 ESTs, homologue of PEM-3 [Oona savigny AW248508 Hs 279727 62 422 5107
425256 collapsm response mediator protein 1 BE297611 Hs 155392 62 2074 6352
416322 pyrrolιne-5 carboxylate reductase 1 BE019494 Hs 79217 62 989 5554
428450 KIAA0175 gene product NM_014791 Hs 1 84339 62 244324446621
448731 ESTs AI522273 Hs 173179 62 4030 7922
452046 KIAA0802 protein AB018345 Hs 27657 62 427542768120
411411 ESTs, Weakly similar to KIAA1330 prate i AA345241 Hs 55950 62 537 5194
410295 nidogen (enactm) AA741357 Hs 356624 62 450 5127
424825 procollagen-lysme, 2-oxoglutarate 5 di AF207069 Hs 153357 61 200520066302
430250 chloride intracellular channel 5 NM.016929 Hs 283021 6 1 2666 2667 6783
407811 cysteine knot superfamily 1, BMP antagr ) AW190902 Hs 40098 6 1 164 4908
458079 Homo sapiens similar to RIKEN cDNA 2810 AI796870 Hs 381220 6 1 4566 8363
401797 Target Exon 61 4663
411962 gbzk85d12 r1 Soares_pregnanLuterus_NbAA09905C 1 61 563 5215
443780 activating transcription factor 5 NM_012068 Hs 9754 6 1 364336447606
417930 Homo sapiens mRNA for KIAA1870 protein, H81136 Hs 334604 6 1 1169 5691
419987 osteomodulin NM 005014 Hs 94070 61 1402 14035868
413945 CD14 antigen NM 000591 Hs 75627 6 1 7587595371
450785 Homo sapiens, alpha-1 (VI) collagen AA852713 Hs 108885 61 4193 8056
444784 ectonucleotide pyrophosphatase/phosphod D12485 Hs 11951 6 1 372437257673
432842 hypothetical protein MGC4485 AW674093 Hs 334822 6 1 2911 6966
452281 Homo sapiens cDNA FLJ11041 fis, clone P T93500 Hs 28792 6 1 4309 8149
443883 serine (or cysteine) proteinase inhibit AA114212 Hs 9930 6 1 3653 7614
433075 sortilin 1 NM 002959 Hs 351872 61 293629376987
440704 insulin-like growth factor binding prot M69241 Hs 162 60 348234837459
414312 ESTs AA155694 Hs 191060 60 800 5407
421913 osteoglycm (osteoinductive factor, mim AI934365 Hs 109439 60 1611 6020
413278 interferoπ-stimulated protein, 15 kDa BE563085 Hs 833 60 695 5322
414657 protein phosphatase 1, regulatory (inhi AA424074 Hs 76780 60 843 5442
448595 KIAA0644 gene product AB014544 Hs 21572 60 401540167910
418067 cystatm E/M AI127958 Hs 83393 60 1189 5706
444931 general transcπption factor II I A AV652066 Hs 75113 60 3735 7681
443105 chondroitm sulfate proteoglycan 4 ( el X96753 Hs 9004 60 36003601 7568
430439 DKFZP434B061 protein AL133561 Hs 380155 60 269526966803
412006 ESTs AW451618 Hs 380683 60 565 5217
452106 ESTs AI141031 Hs 21342 60 4289 8131
416072 growth associated protein 43 AL110370 Hs 79000 60 969 5537
441327 hypothetical protein FLJ10751 AK001706 Hs 7778 60 350935107484
406663 immunoglobulin heavy constant mu U24683 60 39404818
439706 ESTs, Weakly similar to DAP1 HUMAN DEAT AW872527 Hs 59761 60 3421 7404
416433 ESTs AI658904 Hs 84673 60 1004 5566
423225 Thy-1 cell surface antigen AA852604 Hs 125359 60 1786 6148
421487 senne/threonine kinase 23 AF027406 Hs 104865 60 1548 15495975
429903 cyclin dependent kinase 5, regulatory s AL134197 Hs 93597 60 2616 6746
407896 Zic family member 1 (odd paired Drosoph D76435 Hs 41154 60 176 1774919
403903 C5001632* gι|10645308|gblAAG21430 1|ACO 60 4731
425398 hypothetical protein similar to tenasci AL049689 Hs 156369 60 2101 21026370
420059 RAB23, member RAS oncogene family AF161486 Hs 94769 60 1412 14135875
413436 sphingosme kinase 1 AF238083 Hs 68061 60 721 7225339
418299 integrin, beta 2 (antigen CD18 (p95), I AA279530 Hs 83968 60 1212 5725
427239 ubiquitm carrier protein BE270447 Hs 356512 60 2311 6515
428248 ESTs AM 26772 Hs 40479 60 2414 6596
403086 NMJ03319* Homo sapiens titin (TTN), R 59 4705
425280 phosphoenolpyruvate carboxykmase 1 (so U31519 Hs 1872 59 20802081 6357
449378 ESTs AW664026 Hs 59892 59 4085 7967
417114 ESTs AA193472 Hs 20007 59 1080 5621
419968 interleukin 6 (interferon, beta 2) X04430 Hs 93913 59 1399 14005866
408491 ESTs AI088063 Hs 7882 59 230 4961
452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 59 43104311 8150
436748 collagen, type VI, alpha 2 BE159107 Hs 159263 59 3212 7213
426928 retmol dehydrogenase 5 (11-cιs and 9 c AF037062 Hs 172914 59 228522866496
402992 Target Exon 59 4700
428342 Homo sapiens cDNA FLJ13458 fis, clone P AI739168 Hs 349283 59 2432 6611
410628 ESTs, Moderately similar to similar to AI131408 Hs 68756 59 483 5151
451195 mesenchyme homeo box 1 U10492 Hs 438 59 421842198077
437446 ESTs, Moderately similar to CA1 C RAT CO AA788946 Hs 101302 59 3264 7259
424001 paternally expressed 10 W67883 Hs 137476 59 1882 6217
417632 glycoprotein M6B R20855 Hs 379090 59 1141 5667
430171 skin specific protein AF086289 Hs 234766 59 2657 6776
419682 paired like homeodomain transcription f H13139 Hs 92282 59 1368 5841
422567 glypican 6 AF111178 Hs 118407 59 1702 1703 6087
409430 splicing factor, arginine/senne-rich 5 R21945 Hs 346735 59 348 5052
453271 ESTs AA903424 Hs 6786 58 4409 8232
429207 ESTs AA447941 Hs 123423 58 2532 6686
442295 Homo sapiens cDNA FLJ 11 69 fis clone H AI827248 Hs 224398 58 3555 7527
424440 ESTs AA340743 Hs 133208 58 1951 6266
413795 ESTs AL040178 Hs 142003 58 743 5358
424806 MSTP031 protein AA382523 Hs 105689 58 2004 6301
401771 Target Exon 58 4660
450421 ADP nbosyltransferase 3 C03188 Hs 24976 58 4166 8034
426457 chimeπn (chimaeπn) 1 AW894667 Hs 380138 58 2229 6459
429670 protein kinase C, theta L01087 Hs 211593 58 260226036735
456034 gb UI-H-BI3-ala a-12 0-UI s1 NCI_CGAP_S AW45097Ϊ ) 58 4510 8316
421485 hypothetical protein FLJ 10134 AA243499 Hs 104800 58 1547 5974
447217 neuropilm 2 BE465754 Hs 17778 58 3904 7819
410366 hypothetical protein AI267589 Hs 302689 58 457 5133 444143 ESTs, Moderately similar to A56194 thro AW747996 Hs 160999 58 3679 7637
447770 frizzled (Drosophila) homolog 4 AB032417 Hs 19545 58 3961 39627864
427418 LAT1-3TM protein AA402587 Hs 356667 57 2327 6527
439039 ESTs A1656707 Hs48713 57 3373 7356
416908 coagulation factor XIII, A1 polypeptide AA333990 Hs 80424 57 1044 5594
427474 aggrecan 1 (chondroitin sulfate proteog U13192 Hs 2159 57 2334 6532
414285 ESTs AA312914 Hs 71719 57 798 5405
406868 immunoglobulin heavy constant gamma 3 ( AA505445 Hs 300697 57 72 4839
423858 Homo sapiens mRNA, cDNA DKFZp434B0650 ( AL137326 Hs 13348357 1858 6201
414142 hemicent (fibulm 6) AW368397 Hs 334485 57 781 5390
438704 ESTs AI435060 Hs 6705 57 3349 7334
432693 ESTs AW449630 Hs 293790 57 2900 6958
456534 phospholipase C, beta 3, neighbor pseud X91195 Hs 100623 57 4522 8326
440594 ESTs AW445167 Hs 126036 57 3475 7453
409125 axonal transport of synaptic vesicles R17268 Hs 343567 57 308 5024
410867 fibπllm 1 (Marfan syndrome) X63556 Hs 750 57 4984995162
452360 ESTs AI742082 Hs 98539 57 4321 8158
406714 hemoglobin, gamma G AI219304 Hs 266959 57 63 4830
426968 amphiphysin (Stiff-Mann syndrome with b U07616 Hs 1 3034 57 22902291 6499
439551 ESTs W72062 Hs 11112 57 3406 7389
439668 fnzzled (Drosophila) homolog 8 AI091277 Hs 302634 57 3414 7397
403074 NM_003319* Homo sapiens titin (TTN), i mR 57 4703
453596 hypothetical protein FLJ 14834 AA441838 Hs 62905 57 4428 8248
444367 hypothetical protein FLJ22390 H54892 Hs 10974 57 3695 7650
422491 neuronatin AA338548 Hs 117546 57 1691 6077
418283 cathepsm K (pycnodysostosis) S79895 Hs 83942 57 1210 1211 5724
417605 regulator of G-protein signalling 3 AF006609 Hs 82294 57 1138 11395665
404030 NM_015669* Homo sapiens protocadhenn b 57 4735
433124 hypothetical protein SMAP31 U51712 Hs 13775 57 2942 6992
409553 semaphonn Y AF055020 Hs 54937 57 3593605060
419693 FXYD domain-containing ion transport re i AA133749 Hs 301350 57 1371 5844
408829 heparan sulfate (glucosamme) 3-O-sulfo NM 006042 Hs48384 57 2642654991
420486 caveolin 3 AF036365 Hs 98303 57 1456 14575909
428418 ESTs AI368826 Hs 8768 57 2441 6619
425240 phosphoglucomutase 1 AA306495 Hs 1869 56 2071 6350
452242 gycosyltransferase R50956 Hs 159993 56 4305 8145
410132 Mιcrofibrιl-assocιated glycoproteιn-2 NM 003480 Hs 300946 56 4254265110
421848 collagen, type VI, alpha 1 X15880 Hs 108885 56 1602 16036013
425157 phospholipid transfer protein NM 006227 Hs 283007 56 205720586340
448672 ESTs AI955511 Hs 89582 56 4025 7917
419405 ESTs A1377043 Hs 42189 56 1333 5816
439737 Homo sapiens mRNA full length insert cD AI751438 Hs 41271 56 3427 7410
427452 protein phosphatase NM..016364 Hs 1 78170 56 23302331 6529
433635 hypothetical protein MGC12921 AI074502 Hs 134292 56 2994 7032
417511 chordm like AL049176 Hs 82223 56 1125 1126 5657
415701 gamma-glutamyl hydrolase (conjugase, fo NM_003878 Hs 78619 56 940941 5514
438866 tissue inhibitor of metalloproteinase 2 U44385 Hs 6441 56 33603361 7344
453341 adenylyl cyclase-associated protein 2 AI758912 Hs 296341 56 4414 8237
418867 msh (Drosophila) homeo box homolog 2 D31771 Hs 89404 56 1277 12785772
421948 keratin 6A L42583 Hs 334309 56 161816196025
435080 hypothetical protein FLJ 14428 AI831760 Hs 155111 56 3103 7122
412430 fumarylacetoacetate hydrolase (fumaryla i AW675064 Hs 73875 56 584 5233
427019 hypothetical protein FLJ10970 AA001732 Hs 173233 56 2296 6504
449318 Homo sapiens, Similar to RIKEN cDNA 573 AW236021 Hs 78531 56 4080 7962
431347 insulin like growth factor 2 (somatomed A1133461 Hs 251664 56 2774 6859
414020 small inducible cytokine A4 (homologous NM 002984 Hs 75703 55 7677685378
427527 immunoglobulin heavy constant mu AI809057 Hs 153261 55 2340 6536
410036 calsequestππ 2 (cardiac muscle) R57171 Hs 57975 55 412 5100
435520 HNOEL-iso protein AA297990 Hs 9315 55 3130 7146
409893 minichromosome maintenance deficient (S AW247090 Hs 57101 55 397 5088
426485 platelet-derived growth factor receptor NM 006207 Hs 1 70040 55 223822396465
418322 cyclm-dependent kinase inhibitor 3 (CD AA284166 Hs 84113 55 1214 5727
413670 hypothetical protein, expressed in oste AB000115 Hs 75470 55 7357365352
405681 C3000593*gι|10120319|emb|CAC081851| ( 55 4793
421362 hypothetical protein FLJ20043 AK000050 Hs 103853 55 1531 15325965
424125 inhib , beta B (activm AB beta polype M31669 Hs 1735 55 1900 1901 6230
453830 ESTs AA534296 Hs 20953 55 4445 8263
403857 Target Exon 55 4730
431706 adenylyl cyclase-associated protein 2 AI816086 Hs 296341 55 2811 6887
430044 ESTs AA464510 Hs 152812 55 2642 6765
441611 ESTs AW590829 Hs 133463 55 3528 7500
453828 ESTs AW970960 Hs 293821 55 4444 8262
413435 carboxypeptidase E X51405 Hs 75360 55 7197205338
411358 KIAA1691 protein R47479 Hs 94761 55 527 5186
419621 Homo sapiens clone B18 unknown mRNA AF052497 Hs 91626 55 1361 5835
416491 parathyroid hormone receptor 1 U17418 Hs 1019 55 1005 10065567
400297 hypothetical protein DKFZp56401278 AI127076 Hs 288381 55 7 4618
426075 ESTs Weakly similar to 2109260A B cell AW513691 Hs 270149 55 2170 6417
434715 ESTs BE005346 Hs 116410 55 3070 7094
443163 ESTs AI082610 Hs 132079 55 3605 7572
432485 CDW52 antigen (CAMPATH-1 antigen) N90866 Hs 276770 55 2877 6939
425262 GS3955 protein D87119 Hs 155418 55 207620776354
433323 ESTs AA805132 Hs 159142 55 2970 7011
441020 ESTs W79283 Hs 35962 55 3495 7471
419086 Kallmanπ syndrome 1 sequence NM_000216 Hs 89591 54 13001301 5789
420058 Homo sapiens cDNA FLJ10561 fis, clone N AK001423 Hs 94694 54 1411 5874 408901 hypothetical protein FLJ 10468 AK001330 Hs 48855 54 2722734997
406836 immunoglobulin kappa constant AW514501 Hs 156110 54 68 4835
453649 ATPase, Na? transporting, alpha 2 () po Y07494 Hs 34114 54 443244338252
410581 tumor endothelial marker 7 precursor AA018982 Hs 125036 54 478 5146
448988 gamma-aminobutyric acid (GABA) A recept Y09763 Hs 22785 54 405540567940
419750 Homo sapiens cDNA FLJ14236 fis, clone N AL079741 Hs 183114 54 1385 5853
431070 transcπption factor 19 (SC1) AW408164 Hs 249184 54 2744 6837
430147 hairy/enhancer-of-spht related with YR R60704 Hs 234434 54 2652 6773
441689 ESTs AH 23705 Hs 289068 54 3533 7505
416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 54 1001 10025564
443595 PPAR(gamma) angiopoietm related protei AF169312 54 362636277590
438203 ESTs BE540090 Hs 7345 54 3308 7300
419235 neurotrimin AW470411 Hs 288433 54 1320 5804
407785 ESTs, Weakly similar to A43932 muc 2 : AW207285 Hs 98279 54 160 4904
447471 sprouty (Drosophila) homolog 2 AF039843 Hs 18676 54 39303931 7839
432247 ESTs AA531287 Hs 105805 54 2859 6923
447343 ESTs, Highly similar to S02392 alpha 2- AA256641 Hs 236894 54 3916 7828
412507 EphA4 L36645 Hs 73964 54 5965975243
414416 hypothetical protein MGC2721 AW409985 Hs 76084 54 813 5417
427596 extracellular glycoprotein EMILIN-2 pre AA449506 Hs 270143 54 2350 6544
408660 ESTs, Moderately similar to PC4259 fen- AA525775 Hs 89040 54 247 4977
447261 extracellular link domain containing 1 NM 006691 Hs 1 7917 54 390839097823
417421 nuclear receptor subfamily 4, group A, AL138201 Hs 82120 54 1118 5653
426855 Homo sapiens mRNA, cDNA DKFZp566P013(fAL117427 Hs 17277854 2279 6491
451952 ESTs AL120173 Hs 301663 53 4264 8111
447297 protease cysteine, 1 (legumam) BE617970 Hs 18069 53 3914 7826
414459 CCAAT/enhancer binding protein (C/EBP), Y11525 Hs 76171 53 8188195422
444412 Homo sapiens clone HH409 unknown mRNA AI147652 Hs 216381 53 3700 7655
422809 hypothetical protein FLJ10549 AK001379 Hs 121028 53 1741 17426115
448498 ESTs AA418276 Hs 375003 53 4007 7904
441104 ESTs AI382357 Hs 143903 53 3499 7474
427400 hypothetical protein FLJ11939 AW245084 Hs 94229 53 2325 6525
422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 53 1734 6110
441362 RAD51 (S cerevisiae) homolog (E coli R , BE614410 Hs 23044 53 3512 7486
400288 integrin, alpha 5 (fibronectin receptor X06256 Hs 149609 53 1 24614
438086 nuclear receptor subfamily 1 , group I, AA336519 Hs 83623 53 3300 7293
452355 G protein coupled receptor 34 N54926 Hs 29202 53 4320 8157
452056 Homo sapiens, clone IMAGE 4054156, mRNA AW955065 Hs 10115053 4280 8123
414531 allograft inflammatory factor 1 T69387 Hs 76364 53 829 5430
406698 major histocompatibility complex, class X03068 Hs 73931 53 51 524824
445084 hypothetical protein FLJ14761 H38914 Hs 250848 53 3742 7687
418110 hypothetical protein FLJ22202 R43523 Hs 217754 53 1193 5710
408018 ESTs AI912976 Hs 187497 53 185 4927
417160 proteolipid protein 1 (Peli∑aeus Merzba N76497 Hs 355807 53 1086 5626
427099 odd Oz/ten-m homolog 2 (Drosophila mou AB032953 Hs 173560 53 230223036509
453079 LIM protein (similar to rat protein km AW160480 Hs 154103 53 4387 8214
422100 ADP-nbosylatioπ factor-like 7 AI096988 Hs 111554 53 1644 6042
424078 paternally expressed 3 AB006625 Hs 139033 53 1893 18946225
426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 53 2219 6453
407366 gb Homo sapiens cιg33 mRNA, partial seq AF026942 Hs 17518 53 137 4885
428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs 337534 53 2393 6579
422562 AE-bmding protein 1 AI962060 Hs 118397 53 1700 6085
416140 roundabout (axon guidance receptor, Dro AI918035 Hs 301198 53 978 5545
421016 transcπption factor 3 (E2A immuπoglobu AA504583 Hs 101047 53 1497 5937
417259 chondroitin sulfate proteoglycan 2 (ver AW903838 Hs 81800 53 1092 5632
413199 ELAV (embryonic lethal, abnormal vision M62843 Hs 75236 53 6876885317
435256 cytokine like protein C17 AF193766 Hs 13872 53 311631177133
410738 titin AA197128 Hs 172004 53 491 5156
453935 ESTs AI633770 Hs 42572 53 4470 8281
408753 SH3 domain binding glutamic acid rich p AI337192 Hs 47438 53 254 4983
432098 cytochrome P450 retmoid metabolizing p AF252297 Hs 91546 52 283928406908
432503 ESTs AA551196 Hs 188952 52 2878 6940
439999 ras homolog gene family, member E AA115811 Hs 6838 52 3444 7426
425065 Homo sapiens, clone IMAGE 3603836, mRNA AA371906 Hs 294151 52 2042 6329
428834 ESTs AW899713 Hs 10338 52 2479 6647
450923 ESTs AW043951 Hs 38449 52 4203 8063
412563 ESTs, Weakly similar to I38022 hypothet Z25372 Hs 350621 52 605 5250
428976 ras homolog gene family, member I AL037824 Hs 194695 52 2495 6658
407965 heat shock 27kD protein 3 W21483 Hs 41707 52 183 4925
410624 ESTs, Weakly similar to alternatively s AA180060 Hs 68751 52 482 5150
442080 ESTs AW444761 Hs 72901 52 3549 7521
408989 KIAA0746 protein AW361666 Hs 49500 52 290 5010
427700 dual specificity phosphatase 6 AA262294 Hs 180383 52 2361 6554
411020 macrophage receptor with collagenousst NM J06770 Hs 67726 52 5065075168
453767 extracellular matπx protein 2, female AB011792 Hs 35094 52 443944408258
414117 proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs 355807 52 777 5386
424651 ESTs AI493206 Hs 120785 52 1984 6287
407874 Homo sapiens cDNA FLJ14059 fis, clone H AI766311 Hs 289047 52 175 4918
435977 brain-specific membrane anchored protei AL138079 Hs 5012 52 3166 7174
423013 secreted modular calcium binding protei AW875443 Hs 22209 52 1769 6135
423217 collagen, type VII, alpha 1 (epidermoly NM 000094 Hs 1 640 52 1784 17856147
448569 signal transducer and activator of tran BE382657 Hs 21486 52 4014 7909
428862 SRY (sex determining region Y) box 9 (c NM 000346 Hs 2316 52 248324846650
453948 ESTs AI970797 Hs 64859 52 4473 8283
427871 Homo sapiens, clone IMAGE 3507281, mRNA AW992405 Hs 35240652 2380 6568
416729 Ras-related associated with diabetes U46165 Hs 1027 52 1026 10275581 406851 major histocompatibility complex, class AA609784 Hs 352392 52 71 4838
429197 ESTs, Weakly similar to T20272 hypothet H24471 Hs 26930 52 2531 6685
433013 axin 2 (conductm, axil) AI697890 Hs 127337 52 2927 6979
428317 ESTs AW022609 Hs 50745 52 2431 6610
432290 Homo sapiens cDNA FLJ10237 fis, clone H AK001099 Hs 274273 52 2862 6926
422901 nbosomal protein L44 R81936 Hs 75874 52 1757 6126
452698 chemokine (C-C motif) receptor 1 NM 01295 Hs 301921 52 434343448177
410099 KIAA0036 gene product AA081630 Hs 167 52 421 5106
429266 ESTs AI014510 Hs 350621 52 2537 6691
426527 sodium channel, voltage gated, type 1, NM 01037 Hs 1 70238 52 224722486471
403291 Target Exon 52 4713
410494 protein S (alpha) M36564 Hs 64016 51 4664675139
443960 hypothetical protein FLJ21986 AI093577 Hs 255416 5 1 3663 7623
441944 Homo sapiens clone 23767 and 23782 mRNA AW855861 Hs 8025 51 3541 7513
429455 CD209 antigen AI472111 Hs 278694 51 2563 6710
449780 nbosomal protein L44 AA443241 Hs 75874 51 4114 7992
429612 pituitary tumor-transforming 1 AF062649 Hs 252587 51 258625876726
418036 latent transforming growth factor beta Z37976 Hs 83337 5 1 1180 1181 5699
448782 KIAA0758 protein AL050295 Hs 362806 51 403840397928
436481 HSPC150 protein similarto ubiquitm co AA379597 Hs 5199 51 3192 7197
415166 carboxypeptidase Z NM 003652 Hs 78068 5 1 9139145491
415314 glycoprotein M6B N88802 Hs 5422 51 921 5497
439456 hypothetical protein FLJ20980 AI752409 Hs 109314 51 3400 7383
417011 ESTs, Weakly similarto 2109260A B cell F08212 Hs 234898 51 1060 5605
412490 Homo sapiens cDNA FLJ22528 fis, clone AW803564 Hs 288850 51 595 5242
434868 collagen, type VI, alpha 2 R50032 Hs 159263 51 3085 7106
419956 cadheππ 19, type 2 AL137939 Hs 40096 51 1398 5865
438085 ESTs R52518 Hs 7967 51 3299 7292
425964 progesterone membrane binding protein AW889928 Hs 9071 51 2157 6408
418400 KIAA0246 protein BE243026 Hs 301989 51 1234 5739
416051 mannosidase, alpha class 1A, member 1 AA835868 Hs 25253 51 966 5534
445363 tubulm specific chaperone d NMJ05993 Hs 1 2570 51 376237637702
414715 amylo-1,6-glucosιdase, 4-alpha glucanot AA587891 Hs 904 51 855 5450
414945 lymphocyte antigen 6 complex, locus E BE076358 Hs 77667 51 894 5477
425227 ESTs H84455 Hs 40639 5 1 2069 6348
448357 RAB38, member RAS oncogene family N20169 Hs 108923 51 3994 7893
437802 ESTs AI475995 Hs 122910 51 3288 7281
408161 hypothetical protein MGC3032 AW952912 Hs 300383 5 1 195 4937
447519 ESTs U46258 Hs 339665 51 3936 7844
443060 procollagen C-endopeptidase enhancer 2 D78874 Hs 8944 51 3594 7562
423550 ESTs F37675 Hs 152129 51 1815 6169
429583 1-acylglycerol-3 phosphate O-acyltransf NMJ06412 Hs 209119 51 2581 25826723
400263 Eos Control Hs 75309 5 1 4613
452436 ESTs, Moderately similar to A46010 X-li BE077546 Hs 31447 51 4330 8164
411756 discoidm domain receptor family, membe BE294350 Hs 71891 5 1 550 5205
428311 tryptophan 2,3 dioxygeπase NM 005651 Hs 1 83671 51 242924306609
446681 kendnn AJ003624 Hs 15896 51 3869 7789
420028 carbohydrate (N-acetylglucosamine 6 O) AB014680 Hs 8786 5 1 1408 14095872
451292 KIAA1295 protein AB037716 Hs 26204 51 4221 42228079
432306 protein phosphatase 1, regulatory (inhi Y18207 Hs 303090 5 1 286428656928
413063 chitinase 3-lιke 1 (cartilage glycoprot AL035737 Hs 75184 51 676 5308
452689 transferππ F33868 Hs 284176 51 4342 8176
444783 anillin (Drosophila Scraps homolog), ac AK00146B Hs 62180 51 372237237672
402994 NMJ02463* Homo sapiens myxovirus (infl 51 4701
411894 GLI-Kruppel family member GLI3 (Greig c M57609 Hs 72916 51 5595605212
445900 Homo sapiens clone 24787 mRNA sequence AF070526 Hs 125036 5 1 3803 7733
450606 ESTs, Moderately similar to ALU6_HUMAN AI668605 Hs 60380 51 4177 8042
430513 G6C protein AJ012008 Hs 241586 51 270427056809
420162 cyclin dependent kinase 4 BE378432 Hs 95577 5 1 1422 5883
420255 membrane etallo endopeptidase (neutral NM_007289 Hs 1298 50 1438 14395896
423556 dynein, cytoplasmic, heavy polypeptide R72694 Hs 356692 50 1816 6170
417933 thymidylate synthetase X02308 Hs 82962 50 1170 1171 5692
426156 natπuretic peptide receptor A/guaπylat BE244537 Hs 167382 50 2183 6427
427509 complement component 5 receptor 1 (C5a M62505 Hs 2161 50 233823396535
451149 RNA binding motif protein 8B AL047586 Hs 10283 50 4214 8073
422175 ESTs, Highly similar to T00391 hypothet N79885 Hs 6382 50 1657 6053
443062 Homo sapiens mRNA full length insert cD N77999 Hs 8963 50 3595 7563
435099 flap structure-specific endonuclease 1 AC004770 Hs 4756 50 310431057123
436291 protein regulator of cytokinesis 1 BE568452 Hs 344037 50 3180 7185
439070 ESTs A1733278 Hs 7621 50 3375 7358
402855 NM_001839* Homo sapiens calponm 3, i 50 4694
408196 SRY (sex determining region Y) box 22 AL034548 Hs 43627 50 1992004940
426514 bone morphogenetic protein 7 (osteogen I BE616633 Hs 170195 50 2246 6470
421991 KIAA0990 protein NMJ14918 Hs 1 10488 50 1622 16236028
450755 ESTs AA010984 Hs 159464 50 4190 8054
427528 minichromosome maintenance deficient (S AU077143 Hs 179565 50 2341 6537
429150 smoothened (Drosophila) homolog AF120103 Hs 197366 50 251925206677
449129 ESTs AI631602 Hs 258949 50 4066 7950
425863 Human unidentified mRNA, partial sequeπ U43604 Hs 159901 50 2152 6404
415447 myociliπ, trabecular meshwork inducible Z97171 Hs 78454 50 9279285503
422530 bone marrow stromal cell antigen 2 AW972300 Hs 118110 50 1696 6082
422481 DNAX-activatioπ protein 10 AL050163 Hs 117339 50 1687 16886075
435232 cyclin dependent kinase inhibitor 2C (p NMJM262 Hs 4854 50 311431157132
428309 cellular retinoic acid-binding protein M97815 Hs 183650 50 2427 2428 6608
414024 gb zm79g08 r1 Stratagene neuroepitheliu AA134712 Hs 22410 50 769 5379
434355 ESTs AA630865 Hs 186556 50 3049 7076 445160 sine oculis homeobox (Drosophila) homol AI299144 Hs 101937 50 3748 7692
441389 endocytic receptor (macrophage mannose AF134838 Hs 7835 50 351435157488
437696 hypothetical protein dJ37E165 Z83844 Hs 5790 50 3281 7274
421483 hypothetical protein MGC11333 NM_003388 Hs 1 04717 50 1545 15465973
408826 Homo sapiens clone HB-2 mRNA sequence AF216077 Hs 48376 50 263 4990
439332 Homo sapiens mRNA, cDNA DKFZp547M072 (f AW842747 Hs 378821 50 3393 7376
429170 dual specificity phosphatase 4 NM 001394 Hs 2359 50 252425256680
449353 ESTs AA001220 Hs 242947 50 4084 7966
443859 follistatin NM 013409 Hs 9 914 50 3651 36527613
415052 mesenchyme homeo box 2 (growth arrest s NM J05924 Hs 77858 50 9049055485
435905 KIAA0456 protein AW997484 Hs 5003 50 3160 7168
426304 Homo sapiens cDNA FLJ11477 fis, clone H AA374532 Hs 124673 50 2198 6438
436396 wingless-type MMTV integration site fam AI683487 Hs 152213 50 3184 7189
434175 ESTs AW979081 Hs 165469 50 3032 7065
421506 thymidine kinase 1, soluble BE302796 Hs 105097 50 1550 5976
431958 cadhenn 3, type 1, P-cadheπn (placent X63629 Hs 2877 50 283428356904
410600 ESTs, Moderately similarto S65657 alpli i AW575742 Hs 351676 50 479 5147
433043 lymphoid nuclear protein (LAF-4) mRNA W57554 Hs 125019 50 2930 6982
422363 replication factor C (activator 1) 3 (3 T55979 Hs 115474 50 1673 6065
438944 KIAA1444 protein AA302517 Hs 92732 49 3368 7351
411089 cell division cycle 2 like 1 (PITSLRE p AA456454 Hs 214291 49 513 5173
428949 hypothetical protein DKFZp434J0617 AA442153 Hs 104744 49 2490 6655
407204 ESTs, Weakly similar to ALU1 HUMAN ALU R41933 Hs 140237 49 121 4873
409062 Homo sapiens mRNA, cDNA DKFZp564B182 (fAL157488 Hs 50150 49 301 5018
428227 small inducible cytokine subfamily B (C AA321649 Hs 2248 49 2410 6593
428182 ESTs, Weakly similar to GGC1_HUMAN G AN BE386042 Hs 293317 49 2403 6588
417059 extracellular matrix protein 1 AL037672 Hs 81071 49 1067 5611
453597 myo-iπositol 1-phosphate synthase A1 BE281130 Hs 381118 49 4429 8249
423057 ESTs, Moderately similar to I38022 hypo AW961597 Hs 130816 49 1773 6139
422684 H2A histone family, member Z BE561617 Hs 119192 49 1726 6105
432101 EphA3 AI918950 Hs 123642 49 2841 6909
407756 ubiquitm specific protease 18 AA116021 Hs 38260 48 159 4903
424308 minichromosome maintenance deficient (S AW975531 Hs 154443 48 1932 6250
410108 OSBP-related protein 6 AA081659 Hs 318775 48 423 5108
444670 hypothetical protein MGC5370 H58373 Hs 332938 48 3714 7666
427378 melanoma antigen, family D, 1 BE515037 Hs 177556 48 2322 6523
417796 ESTs AA206141 Hs 367818 48 1159 5682
418216 AF15q14 protein AA662240 Hs 283099 48 1206 5721
452973 ESTs H88409 Hs 40527 48 4375 8203
431448 hypothetical protein DKFZp56401278 AL137517 Hs 306201 48 278527866869
434747 ESTs AA837085 Hs 372254 48 3073 7097
435124 ESTs AA725362 Hs 75514 48 3107 7125
414053 transgelm 2 BE391635 Hs 75725 48 774 5383
408938 ESTs AA059013 Hs 22607 48 279 5002
420238 ESTs, Weakly similar to 2109260A B cell AA256783 Hs 12549 48 1436 5894
407656 Homo sapiens mRNA, cDNA DKFZp434B2119 ( AW747986 Hs 37443 48 148 4893
410011 PFTAIRE protein kinase 1 AB020641 Hs 57856 48 4064075096
416640 neuron-specific protein BE262478 Hs 13406 48 1019 5576
453983 ESTs H94997 Hs 16450 48 4476 8286
420842 hypothetical protein MGC10986 AI083668 Hs 50601 48 1485 5929
429707 matrix metalloproteinase 23B W76631 Hs 211819 48 2606 6738
447232 interleukin 10 receptor, alpha AW499834 Hs 327 48 3905 7820
417370 tryptophanyl tRNA synthetase T28651 Hs 374466 48 1105 5643
406672 major histocompatibility complex, class M26041 Hs 198253 48 43444820
448493 ESTs AI524124 Hs 270307 47 4006 7903
445302 hypothetical protein FLJ 10675 AK001537 Hs 12488 47 375737587699
451598 ESTs N29102 Hs 79658 47 4241 8093
434629 glioma amplified sequence 41 AA789081 Hs 4029 47 3064 7090
439130 ESTs AA306090 Hs 345588 47 3378 7361
443247 c-Myc target JP01 BE614387 Hs 333893 47 3611 7578
432481 introπ of collagen, type XI, alpha 1 AW451645 Hs 151504 47 2876 6938
417115 small nuclear πbonucleoprotein polypep AW952792 Hs 334612 47 1081 5622
412564 cardiac ankyπn repeat protein X83703 Hs 355934 47 6066075251
429139 ESTs F09092 Hs 66087 47 2517 6675
424829 nerve growth factor receptor (TNFRsupe NMJ02507 Hs 1 827 47 20072008 6303
427647 Homo sapiens cDNA FLJ20653 fis, clone K W19744 Hs 180059 47 2354 6548
408482 adenosine A2b receptor NM_000676 Hs 45743 47 2262274959
440028 ESTs, Weakly similar to T17227 hypothet AW473675 Hs 367649 47 3446 7428
432527 ESTs AW975028 Hs 102754 47 2883 6944
449595 ESTs AW293799 Hs 255238 46 4098 7979
454071 ESTs AI041793 Hs 42502 46 4487 8295
428977 cyclin B2 AK001404 Hs 194698 46 2496 6659
424263 L1 cell adhesion molecule (hydrocephalu M77640 Hs 1757 46 1925 19266246
412939 eukaryotic translation elongation facto AW411491 Hs 75069 46 657 5292
410342 Fc fragment of IgE, high affinity I, re R31350 Hs 743 46 453 5129
433513 ESTs AI566356 Hs 171437 46 2985 7024
452613 ESTs AA461599 Hs 23459 46 4337 8171
427876 ESTs AI494291 Hs 369171 46 2381 6569
453139 Human DNA sequence from clone RP11-234G AA330620 Hs 348805 46 4394 8220
431124 doublesex and mab 3 related transcnpti AF284221 Hs 59506 46 275327546843
406636 gb Homo sapiens (clone WR4 12VL) anti-t L12064 46 32 33 4814
456181 ras inhibitor L36463 Hs 1030 46 451645178321
408209 ets variant gene 5 (ets-related molecul NM 004454 Hs 43697 46 2042054944
418452 C-type (calcium dependent carbohydrate i BE379749 Hs 85201 46 1241 5744
419726 bone morphogenetic protein 1 U50330 Hs 1274 46 1376 13775848
449077 ESTs AW262836 Hs 252844 46 4063 7947 427585 collagen, typeX, alpha 1 (Schmid metap D31152 Hs 179729 46 23496543 438937 ESTs AW952654 Hs 73964 45 33677350 433819 ESTs AW511097 Hs 110069 45 30077042 430223 nephroblastoma overexpressed gene NMJ02514 Hs 235935 45 266126626779 449294 ESTs A1651786 Hs 195045 45 40797961 419488 nucleophosmm/nucleoplasmin 3 AA316241 Hs 90691 45 13425822 409637 Homo sapiens mRNA, cDNA DKFZp434K0621 ( AA323948 Hs 55407 45 3725069 417166 Paired box protein Pax-3 AA431323 Hs 42146 45 10885628 410407 carbonic anhydrase IX X66839 Hs 63287 45 4604615135 452402 peroxisome proliferative activated rece AI138530 Hs 22216 45 43278162 424223 putative DNA/chromatm binding motif AJ243706 Hs 143323 45 191519166240 433212 ESTs BE218049 Hs 121820 45 29567001 421251 enigma (LIM domain protein) Z28913 Hs 102948 45 15215957 416700 cathepsm D (lysosomal aspartyl proteas AW498958 Hs 343475 45 10235579 452839 nbosomal protein L44 R96290 Hs 75874 44 43598189 445875 Homo sapiens clone 24453 mRNA sequence AF070524 Hs 13410 44 38017731 425848 valyl-tRNA synthetase 2 BE242709 Hs 159637 44 21506402 451304 collagen, type XVI, alpha 1 M92642 Hs 26208 44 422442258081 435854 putative ankyπn repeat containing prot AJ278120 Hs 4996 44 315731587166 413916 apolipoprotein C-ll N49813 Hs 75615 44 7535367 440099 DKFZP564G202 protein AL080058 Hs 6909 44 345334547434 427674 H2B histone family, member Q NM 003528 Hs 2 178 44 235923606553 423811 homeo box C4 AW299598 Hs 50895 44 18546198 453883 cofactor required for Sp1 transcription AI638516 Hs 347524 43 44598273 422515 multifunctional polypeptide similar to AW500470 Hs 117950 43 16936079 442173 KIAA0144 gene product N76101 Hs 8127 43 35527524 451763 hypothetical protein FLJ14220 AW294647 Hs 233634 43 42548103 448961 ESTs AI610643 Hs 187285 43 40527937 421815 membrane protein CH1 AW592146 Hs 108636 43 15986009 421920 gamma-aminobutyπc acid (GABA) receptor BE551245 Hs 1438 43 16146022 451099 interleukin 13 receptor, alpha 2 R52795 Hs 25954 43 42128071 428865 BarH-like homeobox 1 BE544095 Hs 164960 43 24856651 413385 indoleamme-pyrrole 2,3 dioxygeπase M34455 Hs 840 43 7107115331 421535 phosphoπbosylformylglycinamidme synth AB002359 Hs 105478 42 155715585981 417355 endothelm receptor type B D13168 Hs 82002 42 110011015640 432691 mitogen-activated protein kinase 7 U29725 Hs 3080 42 289728986956 435652 uncharacteπzed hypothalamus protein HB N32388 Hs 334370 42 31427154 419093 spinal cord-derived growth factor-B AI804054 Hs 112885 42 13045792 441544 ESTs AW300043 Hs 127137 42 35237496 437044 differentially expressed in Fancom's a AL035864 Hs 69517 42 32337232 419236 Homo sapiens cDNA FLH 1481 fis clone H VAA330447 Hs 135159 41 13215805 428242 leukemia inhibitory factor (cholmergic H55709 Hs 2250 41 24116594 433570 ESTs, Weakly similar to S55916 nbosoma AI580053 Hs 109007 41 29887027 430838 hypothetical protein FLJ12015 N46664 Hs 169395 41 27336829 424291 ephrιn-B1 AL120051 Hs 144700 41 19316249 448425 ESTs AI500359 Hs 371249 41 40047901 426798 ESTs AA385062 Hs 130260 41 22756487 432994 ESTs AA573452 Hs 150941 41 29226976 442285 uncharactenzed hypothalamus protein HT W28729 Hs 374989 41 35547526 403171 C2001472* gι|5809678|gb|AAB418482| (U6 40 4710 457458 ESTs AW972881 Hs 276507 40 45528352 451698 endothelm converting enzyme-like 1 Y16187 Hs 26880 39 424942508100 417437 interferon regulatory factor 4 U52682 Hs 82132 39 112311245656 404815 ENSP00000251989* DJ100N221 (NOVEL EGF- 39 4761 452319 transducm like enhancer of split 1 , ho M99435 Hs 28935 37 431343148152 424326 ADAM-like disintegnn protease, decysin NM_014479 Hs 1 45296 37 193419356252 407178 AP-2 beta transcnption factor AA195651 Hs 352312 36 118 4870 419762 ESTs A1608647 Hs 32374 35 1387 5855 414477 amplified in osteosarcoma U41635 Hs 76228 35 8228235425 412709 KIAA0027 protein AL022327 Hs 74518 33 631 6325269 453665 ESTs, Weakly similar to SFRB_HUMAN SPLI AA626250 Hs 326184 31 4434 8253 429329 ESTs AA456140 Hs 99235 31 2547 6699 429921 collagen, type XI, alpha 1 AA526911 Hs 82772 31 2620 6749 406367 NMJ22357 Homo sapiens putative melallo 31 4804
TABLE 7B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
459702 539529 BG207209 BE166299 A1204995 BG199355 AW969908 AA528756 AW440776 BI044354
414315 203914_2 AA494098 Z24878 F13654 AA494040
418059 1164438J AA211586 F35799 F29720 AW937408 AW937387 AA211641
411962 2307710 AA099050AA099526 T47733
456034 685586J AA136653 AA136656 AW450979 AA984358 AA809054 AW238038 AA492073 BE168945
426413 372468 1 AW954494 AA377823 BG219617 BG195685 BG616269 AI022688
406636 0_0 L12064 L12083 L12065 L12075 L12066 L12085 L12072 L12082 L12081 L12062 L12080
TABLE 7C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers "Dunham I et al refers to the publication entitled
"The DNA sequence of human chromosome 22 Dunham I et al , Nature (1999) 402489 495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand Nt_posιtιon
405001 6015406 Minus 104646-104819
404977 3738341 Minus 43081-43229
403088 8954241 Plus 169894-170193,170504-170806
400499 9796071 Minus 148495-148806
403593 6862650 Minus 62554-62712,69449-69602
400651 8117978 Minus 81488-81646
401781 7249190 Minus 83215-83435,83531-83656,83740-83901,8423
401780 7249190 Minus 28397-28617,28920-29045,29135-29296,2941
403071 8954241 Plus 136688-137096
403081 8954241 Plus 155749-156048,156142-156459
401203 9743387 Minus 172961-173056,173868-173928
403087 8954241 Plus 169511-169795
406519 3962489 Plus 34617-34928
402621 9930950 Plus 130806-131036
406387 9256180 Plus 116229-116371,117512-117651
401797 6730720 Plus 6973-7118
403903 7710671 Minus 101165-102597
403086 8954241 Plus 169170-169412
402992 7767907 Minus 42137-42515
401771 9966243 Plus 166897-167099
403074 8954241 Plus 143375-143561
404030 7671252 Plus 149362-151749
405681 4544348 Minus 79420-79605
403857 7708910 Minus 2524-3408
403291 7230870 Plus 95177-95435
402994 2996643 Minus 4727-4969
402855 9662953 Minus 59763-59909
403171 9838164 Minus 74502-74703
404815 5911819 Minus 64494-64691
406367 9256126 Minus 58313-58489
TABLE 8A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of soft tissue sarcoma AIs divided by the 50th percentile of normal soft tissue AIs, whei subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name Accession UniGene RATIO SEQ ID #
413778 myosin, light polypeptide 2, regulatory AA090235 Hs 75535 296 740 5356
409601 keratin 1 (epide1 rmolytic hyperkeratosis AF237621 Hs 80828 241 3653665064
425545 Homo sapiens, clone MGC 12401, mRNA, co N98529 Hs 158295 21 9 2114 6379
417153 collagen, type II, alpha 1 (pπmary ost X57010 Hs 81343 21 5 1084 10855625
426300 delta like homolog (Drosophila) U15979 Hs 169228 207 219621976437
441134 cellular retmoic acid-binding protein W29092 Hs 346950 206 3500 7475
439496 Homo sapiens, Similar to RI EN cDNA 111 BE616501 Hs 32343 197 3402 7385
431103 pleiotrophm (hepaπn binding growth fa M57399 Hs 44 193 274827496840
426752 titin X69490 Hs 172004 191 226622676482
412519 troponin T1, skeletal, slow AA196241 Hs 73980 186 598 5244
422424 prostate differentiation factor AI186431 Hs 296638 174 1681 6070
452838 preferentially expressed antigen in mel U65011 Hs 30743 169 435743588188
406704 myosin, heavy polypeptide 7, cardiac mu M21665 Hs 929 169 55564826
400440 nebulm X83957 Hs 83870 165 24254627
407013 gb Human nebulm mRNA, partial eds U35637 Hs 83870 162 94954851
406687 matrix metalloproteinase 11 (stromelysi M31126 Hs 352054 158 49504823
424687 matrix metalloproteinase 9 (gelatinase J05070 Hs 151738 157 1986 19876289
407245 titin X90568 Hs 172004 151 132 1334881
422640 troponin C slow i M37984 Hs 118845 150 1718 17196099
432874 melanoma inhibitory activity W94322 Hs 279651 149 2913 6968
414219 ALL1-fused gene from chromosome 1q W20010 Hs 75823 148 789 5397
448731 ESTs AI522273 Hs 173179 147 4030 7922
453857 Ras-mduced senescence 1 (RIS1) AL080235 Hs 35861 145 44494450 8266
420783 lectin, galactoside binding, soluble, 7 AI659838 Hs 99923 144 1478 5924
417070 titin Z19077 Hs 172004 144 1070 5614
428305 cartilage linking protein 1 AA446628 Hs 2799 143 2426 6607
429359 matrix metalloproteinase 14 (membrane-l W00482 Hs 2399 139 2551 6702
426600 VGF nerve growth factor inducible NMJJ03378 Hs 1 71014 135 22552256 6475
417389 midkine (neunte growth-promoting facto BE260964 Hs 82045 133 1109 5647
422069 tit -cap (telethonm) AJ010063 Hs 343603 129 1635 16366037
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 128 1162 5685
419875 proenkephal AA853410 Hs 93557 127 1391 5859
413278 interferon stimulated protein 15 kDa BE563085 Hs 833 124 695 5322
416373 ESTs, Weakly similar to S12658 cysteine AA195845 Hs 73680 124 996 5559
413031 phosphofructokmase, muscle BE515051 Hs 75160 124 671 5304
427335 G antigen 7B AA448542 Hs 278444 123 2317 6520
421773 ESTs W69233 Hs 112457 12 1 1588 6000
440274 scrapie responsive protein 1 R24595 Hs 7122 11 9 3464 7443
422887 ESTs AI751848 Hs 49215 11 8 1755 6124
418678 caπcer/testis antigen (NY-ESO-1) NM_001327 Hs 8 7225 11 8 1269 12705765 422106 Fc fragment of IgG binding protein D84239 Hs 111732 11 8 1646 16476044 450098 hypothetical protein FLJ21080 W27249 Hs 8109 11 7 4134 8009 422871 collagen, type XI, alpha 2 AL031228 Hs 121509 11 7 175317546123 417308 KIAA0101 gene product H60720 Hs 81892 11 7 1094 5634 438549 tnnucleotide repeat containing 3 BE386801 Hs 21858 11 6 3331 7320 448719 tπnucleotide repeat containing 3 AA033627 Hs 21858 11 5 4028 7920 405001 interleukin enhancer binding factor 1 11 3 4767 452620 ESTs AA436504 Hs 119286 11 3 4338 8172 413554 secretogranm II (chromogranm C) AA319146 Hs 75426 11 2 729 5346 431553 cartilage linking protein 1 X78075 Hs 2799 11 2 2792 6874 418399 hypothetical protein FLJ12442 AF131781 Hs 84753 11 2 1232 12335738 417515 aiaxia-telangiectasia group D-associate L24203 Hs 82237 11 1 1129 11305659 431211 gap junction protein, beta 2, 26kD (con M86849 Hs 323733 109 276227636850 422599 non metastatic cells 1, protein (NM23A) BE387202 Hs 118638 108 1710 6092 428411 ESTs AW291464 Hs 10338 108 2439 6617 425247 matrix metalloproteinase 11 (stromelysi NM 005940 Hs 1 55324 107 207220736351 420208 silver (mouse homolog) like BE276055 Hs 95972 107 1431 5891 419741 Ubiquitm carrier protein E2-C NM 007019 Hs 93002 106 1379 13805850 431360 loπcnn NMJ00427 Hs 251680 106 277627776861 425308 receptor tyrosine kinase like orphan re M97639 Hs 155585 106 208720886362 425154 collagen, type IX, alpha 1 NMJ01851 Hs 1 54850 105 205520566339 404977 Insulin-like growth factor 2 (somatomed 104 4766 440099 DKFZP564G202 protein AL080058 Hs 6909 104 345334547434 428311 tryptophan 2,3 dioxygenase NMJ05651 Hs 1 83671 103 242924306609 434060 hypothetical protein PR01489 AA744902 Hs 197922 103 3025 7058 410621 titin AA194329 Hs 172004 101 481 5149 428398 ESTs AI249368 Hs 98558 10 1 2435 6614 447377 transcription factor AP-2 alpha X77343 Hs 334334 10 1 39203921 7831 419550 KIAA0128 protein, septin 2 D50918 Hs 90998 100 1348 13495827 429294 Homo sapiens cDNA FLJ22463 fis, clone AA095971 Hs 198793 100 2540 6693 412636 desmoplakm (DPI, DPII) NM.004415 Hs 349499 100 6186195259 427666 calmoduliπ like skin protein (CLSP) AI791495 Hs 180142 99 2356 6550 419762 ESTs AI608647 Hs 32374 99 1387 5855 449048 similar to S68401 (cattle) glucose indu Z45051 Hs 22920 98 4061 7945 401781 Target Exon 98 4662 405443 Target Exon 98 4782 428248 ESTs AI126772 Hs 40479 97 2414 6596 450375 a disintegnn and metalloproteinase dom AA009647 Hs 352537 97 4159 8028 409169 (clone PWHLC2-24) myosin light chain 2 F00991 Hs 50889 97 316 5029 416658 fibπllin 2 (congenital contractural ar U03272 Hs 79432 96 1020 1021 5577 439180 v erb-b2 avian erythroblastic leukemia AI393742 Hs 199067 96 3380 7363 417333 bromodomain and PHD finger containing , AL157545 Hs 173179 96 1096 5636 415166 carboxypeptidase Z NMJ03652 Hs 78068 96 913 9145491 403088 NMJ03319* Homo sapiens Win (TTN), i TIR 95 4707 418391 troponin I, skeletal, slow NM 003281 Hs 84673 95 1228 12295736 427863 MLL sept -like fusion AF189712 Hs 181002 95 237823796567 440704 insulin like growth factor binding prot M69241 Hs 162 94 348234837459 414024 gb zm79g08 r1 Stratagene neuroepitheliu AA134712 Hs 22410 94 769 5379 417930 Homo sapiens mRNA for KIAA1870 protein, H81136 Hs 334604 94 1169 5691 424825 procollagen-lysine, 2-oxoglutarate 5 di AF207069 Hs 153357 94 200520066302 421733 fibroblast growth factor receptor 3 (ac AL119671 Hs 1420 93 1585 5997 406707 myosin, heavy polypeptide 2, skeletal m S73840 Hs 931 93 61 624829 445016 reelm U79716 Hs 12246 93 3738 37397684 409125 axonal transport of synaptic vesicles R17268 Hs 343567 93 308 5024 421116 ret ol binding protein 1, cellular T19132 Hs 101850 92 1508 5947 416349 myomesin (M protein) 2 (165kD) X69089 Hs 79227 92 991 9925556 417689 KIAA0128 protein, septin 2 AA828347 Hs 90998 92 1148 5673 456508 ESTs, Weakly similar to AF208855 1 BM 0AA502764 Hs 123469 9 1 4521 8325 435968 integral membrane protein 3 AW161481 Hs 111577 9 1 3165 7173 428405 cholmergic receptor, nicot ic, alpha Y00762 Hs 2266 91 243624376615 415989 ESTs AI267700 Hs 351201 90 962 5530 443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 90 3621 36227586 453597 myo inositol 1-phosphate synthase A1 BE281130 Hs 381118 90 4429 8249 421815 membrane protein CH1 AW592146 Hs 108636 90 1598 6009 434352 small muscle protein, X-lmked AF129505 Hs 86492 89 304730487075 452223 hypothetical protein MGC2827 AA425467 Hs 8035 89 4302 8142 409178 kallikrein 5 BE393948 Hs 50915 89 319 5032 418140 microfibπllar-associated protein 2 BE613836 Hs 83551 88 1196 5713 418113 SRY (sex determining region Y) box 4 AI272141 Hs 83484 88 1194 5711 408915 heptacellular carcinoma novel gene 3 pr NM 016651 Hs 48950 88 2742754998 412719 ESTs AW016610 Hs 816 87 633 5270 458079 Homo sapiens similar to RIKEN cDNA 2810 AI796870 Hs 381220 87 4566 8363 412276 macrophage migration inhibitory factor BE262621 Hs 73798 86 580 5229 428087 troponin C2, fast AA100573 Hs 182421 86 2396 6582 433447 neuronal pentraxm II U29195 Hs 3281 86 29802981 7021 428928 cadhenn 1, type 1, E-cadheπn (epithel BE409838 Hs 194657 85 2489 6654 416072 growth associated protein 43 AL110370 Hs 79000 85 969 5537 414416 hypothetical protein MGC2721 AW409985 Hs 76084 85 813 5417 418390 Win immunoglobulin domain protein (my AF133820 Hs 84665 85 1226 12275735 442573 branched chain ammotransferase 1, cyto H93366 Hs 7567 85 3570 7541 450447 hypothetical protein P15 2 AF212223 Hs 25010 85 416841698036 417435 carbonic anhydrase III, muscle specific NMJ05181 Hs 82129 84 1121 11225655 402992 Target Exon 84 4700 421579 stem cell growth factor, lymphocyte sec NM_002975 Hs 1 05927 84 1567 15685987 422633 enolase 3, (beta muscle) X56832 Hs 118804 84 1716 17176098 457411 iroquois-class homeobox protein IRX2 AW085961 Hs 130093 83 4549 8349 409103 XAGE-1 protein AF251237 Hs 112208 83 3043055021
417409 syndecan 1 BE272506 Hs 82109 83 1113 5650
428484 solute carrier family 7 (cationic ammo AF104032 Hs 184601 83 24492450 6624
412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 83 569 5220
417900 CDC20 (cell division cycle 20, S cerev BE250127 Hs 82906 83 1165 5688
449722 cyclin B1 BE280074 Hs 23960 82 4112 7990
425227 ESTs H84455 Hs 40639 82 2069 6348
414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 82 8768775465
407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 82 166 4910
418067 cystatm E/M AI127958 Hs 83393 82 1189 5706
457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 82 4561 8359
409633 ESTs AW449822 Hs 55200 81 371 5068
412926 macrophage myπstoylated alanine-nch C AI879076 Hs 75061 8 1 655 5290
426429 myosin-bmding protein C, slow-type X73114 Hs 169849 81 22242225 6456
440042 ESTs AI073387 Hs 133898 81 3448 7430
441636 Homo sapiens mRNA, cDNA DKFZp566E183 (f AA081846 Hs 7921 81 3530 7502
421458 carbohydrate (keratan sulfate Gal-6) su NM 003654 Hs 1 04576 80 1543 15445972
427239 ubiquitm earner protein BE270447 Hs 356512 80 2311 6515
413511 arginine πch, mutated in early stage t AI627178 Hs 75412 80 728 5345
411296 growth suppressor 1 BE207307 Hs 10114 80 524 5183
439979 hypothetical protein FLJ 10430 AW600291 Hs 6823 80 3442 7424
423575 intran of peπostin (OSF-2os) C18863 Hs 163443 79 1820 6173
454140 hypothetical protein FLJ10474 AB040888 Hs 41793 79 449344948301
428182 ESTs, Weakly similar to GGC1_HUMAN G AN BE386042 Hs 293317 79 2403 6588
440087 hypothetical protein FLJ22678 W28969 Hs 7718 79 3452 7433
425234 ESTs, Weakly similarto I38022 hypothe AW152225 Hs 165909 78 2070 6349
400231 Eos Control Hs 169476 78 4603
407619 collagen, type IX, alpha 2 AL050341 Hs 37165 78 146 1474892
410366 hypothetical protein AI267589 Hs 302689 78 457 5133
406837 immunoglobulin kappa constant R70292 Hs 156110 78 69 4836
406782 gb zw20f11 s1 Soares ovary tumor NbHOT AA430373 78 65 4832
431629 interferon, alpha inducible protein (cl AU077025 Hs 265827 78 2803 6881
422867 cartilage oligomenc matπx protein (ps L32137 Hs 1584 78 1751 17526122
408989 KIAA0746 protein AW361666 Hs 49500 78 290 5010
420798 keratin 10 (epidermolytic hyperkeratosi W93774 Hs 99936 77 1479 5925
427378 melanoma antigen, family D, 1 BE515037 Hs 177556 77 2322 6523
409041 Hypothetical protein, XP_051860 (KIAA11 AB033025 Hs 50081 77 299 3005017
447033 Predicted gene Eos cloned, secreted w/ AI357412 Hs 157601 77 3885 7802
423217 collagen, type VII, alpha 1 (epidermoly NMJ00094 Hs 1 640 77 178417856147
409096 sarcomenc muscle protein AA194412 Hs 50550 77 302 5019
418506 Unknown protein for MGC 29643 (formerly AA084248 Hs 372651 77 1247 5748
414152 thrombospondm 4 NM 003248 Hs 75774 77 7827835391
412140 RAB6 interacting, kmesin-like (rabkine AA219691 Hs 73625 77 573 5223
401780 NM_005557* Homo sapiens keratin 16 ( oc 77 4661
437696 hypothetical protein dJ37E165 Z83844 Hs 5790 76 3281 7274
431958 cadhenn 3, type 1, P-cadheππ (placent X63629 Hs 2877 76 283428356904
433075 sortilm 1 NM 002959 Hs 351872 76 293629376987
427747 serine/threon e kinase 12 AW411425 Hs 180655 76 2365 6557
444006 type I transmembrane protein Fn14 BE395085 Hs 334762 76 3668 7627
416378 ankyππ repeat domain 2 (stretch respon AW044467 Hs 73708 76 997 5560
409327 collagen, type IX, alpha 3 L41162 Hs 53563 76 341 3425047
429329 Homo sapiens pannexm 3 (PANX3) AA456140 Hs 99235 75 2547 6699
432481 intron of collagen, type XI, alpha 1 AW451645 Hs 151504 75 2876 6938
427474 aggrecan 1 (chondroitin sulfate proteog U13192 Hs 2159 75 2334 6532
436481 HSPC150 protein similar to ubiquitm co AA379597 Hs 5199 75 3192 7197
426363 transforming growth factor, beta 3 M58524 Hs 2025 75 22102211 6446
451099 interleukin 13 receptor, alpha 2 R52795 Hs 25954 75 4212 8071
440650 Human DNA sequence from PAC 75N13 on ch R4469; ! Hs 326801 75 3477 7455
408536 ESTs AW381532 Hs 135188 75 236 4967
412641 heat shock 90kD protein 1 , beta M16660 Hs 74335 75 620621 5260
421016 transcription factor 3 (E2A immunoglobu AA504583 Hs 101047 74 1497 5937
438746 Human melanoma associated antigen p97 (AI885815 Hs 184727 74 3353 7337
426509 pentaxm-related gene, rapidly induced M31166 Hs 2050 74 2243 22446468
439755 B7 homolog 3 AW748482 Hs 77873 74 3430 7413
453392 SRY (sex determining region Y)-box 11 U23752 Hs 32964 74 441644178239
418203 CDC28 protein kinase 2 X54942 Hs 83758 74 1202 12035719
412006 ESTs AW451618 Hs 380683 73 565 5217
414945 lymphocyte antigen 6 complex, locus E BE076358 Hs 77667 73 894 5477
407656 Homo sapiens mRNA cDNA DKFZp434B2119 (AW747986 Hs 37443 73 148 4893
438949 abl-mteractor 12 (SH3 containing prate AA058571 Hs 285728 73 3369 7352
413436 sphingosme kinase 1 AF238083 Hs 68061 73 721 7225339
410001 kallikrein 11 AB041036 Hs 57771 73 4034045094
435793 KIAA1313 protein AB037734 Hs 4993 73 31523153 7162
446051 ephπn-A3 BE048061 Hs 37054 73 3816 7744
426440 solute carrier family 2 (facilitated gl BE382756 Hs 169902 73 2228 6458
444371 forkhead box Ml BE540274 Hs 239 73 3696 7651
449294 ESTs AI651786 Hs 195045 73 4079 7961
401673 C16001416* gι|12743112|ref|XP_010131 2| 72 4658
401797 Target Exon 72 4663
412755 ESTs, Weakly similar to P4HAJHUMAN PROL BE144306 Hs 179891 72 637 5274
424415 eπolase 2, (gamma, neuronal) NMJJ01975 Hs 1 46580 72 1947 1948 6263
401566 NM_005159 Homo sapiens actin, alpha, ca 72 4654
430713 eukaryotic translation elongation facto AA351647 Hs 2642 72 2726 6824
432239 matrix metalloproteinase 13 (collagenas X81334 Hs 2936 72 28562857 6921
438682 EBP50-PDZ ιπteractorof 64 kD AA354489 Hs 17719 72 3346 7331
412939 eukaryotic translation elongation facto AW411491 Hs 75069 72 657 5292 453665 ESTs, WeaklysimilartoSFRB_HUMAN SPLI AA626250 Hs 326184 72 44348253 428471 stratifin X57348 Hs 184510 7 2 244524466622 409893 minichromosome maintenance deficient (S AW247090 Hs 57101 7 2 3975088 425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 7 2 209921006369 449226 KIAA0367 protein AB002365 Hs 23311 7 2 407240737955 421717 divalent cation tolerant protein CUTA AF230924 Hs 107187 72 158315845996 437898 ESTs W81260 Hs 43410 7 1 32937286 413011 biglycaπ AW068115 Hs821 7 1 6695302 421307 Homo sapiens mRNA, cDNA DKFZp434B0425 ( BE539976 Hs 10330571 15285963 435652 uncharacterized hypothalamus protein HB N32388 Hs 334370 7 1 31427154 418322 cyclin dependent kinase inhibitor 3 (CD AA284166 Hs 84113 71 12145727 453876 ESTs, Weakly similar to I38022 hypothet AW021748 Hs 110406 71 44578271 444026 hypothetical protein FLJ14957 AA205759 Hs 10119 71 36727631 421508 absent in melanoma 2 NM_004833 Hs 1 05115 71 155115525977 426798 ESTs AA385062 Hs 130260 71 22756487 436608 down syndrome critical region protein D AA628980 Hs 192371 70 32057207 436748 collagen, type VI, alpha 2 BE159107 Hs 159263 70 32127213 420103 aldehyde dehydrogenase 1 family, member AA382259 Hs 95197 70 14165878 453830 ESTs AA534296 Hs 20953 70 44458263 422043 retmoic acid induced 1 AL133649 Hs 110953 70 162916306033 419222 spermme synthase AD001528 Hs 89718 70 131813195803 427099 odd Oz ten-m homolog 2 (Drosophila, ou AB032953 Hs 173560 70 230223036509 414346 splicing factor 3b, subunit 2, 145kD AL035770 Hs 75916 70 8065411 411089 cell division cycle 2-lιke 1 (PITSLRE p AA456454 Hs 214291 70 5135173 407811 cysteine knot superfamily 1 , BMP antago AW190902 Hs 40098 70 1644908 415314 glycoprotein M6B N88802 Hs 5422 69 9215497 407792 putative secreted ligand homologous to AI077715 Hs 39384 69 1624906 424001 paternally expressed 10 W67883 Hs 137476 69 18826217 400499 C10001858 gι|6679124|reflNP 032759 1| n 69 4628 446142 ESTs AI754693 Hs 145968 69 38207748 408988 Homo sapiens clone TUA8 Cn du chat reg AL119844 Hs 49476 69 2895009 412974 emopamil binding protein (sterol isomer R18978 Hs 75105 69 6645297 411410 lamimn, gamma 3 R20693 Hs 69954 69 5365193 425256 collapsm response mediator protein 1 BE297611 Hs 155392 69 20746352 427171 NIPSNAP, C elegans, homolog 1 AJ001258 Hs 173878 69 230723086512 421406 Meis (mouse) homolog 2 AF179897 Hs 104105 69 154115425971 451934 ESTs AI540842 Hs 61082 69 42628109 433487 histone deacetylase 2 U31814 Hs 3352 69 298329847023 411852 ESTs, Weakly similar to T00329 hypothet AA528140 Hs 107515 68 5555208 415752 putative transmembrane protein BE314524 Hs 78776 68 9455517 429259 Plakophilm AA420450 Hs 380088 25356689 448357 RAB38, member RAS oncogene family N20169 Hs 108923 39947893 451766 ephnn B3 NMJ01406 Hs 26988 425542568104 416322 pyrrolme 5-carboxylate reductase 1 BE019494 Hs 79217 68 9895554 447646 Homo sapιens mRNAfor KIAA1753 proteιn, BE619752 Hs 66053 68 39457852 413916 apolipoprotein C-ll N49813 HHss 7755661155 6688 7535367 414806 phosphatidylsenne synthase 1 D14694 Hs 77329 68 8718725462 418478 cyclm-dependent kinase inhibitor 2A (m U38945 Hs 1174 6 8 124512465747 433577 ESTs AW007080 Hs 284192 68 29897028 451811 hypothetical protein MGC1136 AA663485 Hs 8719 6 8 42598106 429345 hypothetical protein R11141 Hs 199695 25486700 433101 Homo sapiens mRNA, cDNA DKFZp566L203 (f AW572317 Hs 12082 68 29406990 430413 small inducible cytokine A5 (RANTES) AW842182 Hs 241392 67 26936801 426457 chimeπn (chimaeπn) 1 AW894667 Hs 380138 67 22296459 418418 ESTs R61527 Hs 237517 67 12385742 426831 S-adenosylhomocysteme hydrolase BE296216 Hs 172673 67 22786490 432179 EphB3 X75208 Hs 2913 67 284928506915 412709 KIAA0027 protein AL022327 Hs 74518 67 6316325269 421707 lectomedιn-2 NMJ314921 Hs 1 07054 67 158115825995 435066 dyskeratosιs congenιta 1, dyskeπn BE261750 Hs 4747 67 31027121 442577 ESTs AA292998 Hs 163900 66 35717542 442923 ESTs, Weakly similar to unnamed protein AW248322 Hs 95835 66 35907558 427528 minichromosome maintenance deficient (S AU077143 Hs 179565 66 2341 6537 423739 ESTs AA398155 Hs 97600 18426190 449780 nbosomal protein L44 AA443241 Hs 75874 66 41147992 433972 cisplatm resistance-associated overexp AI878910 Hs 278670 66 30217054 406868 immunoglobulin heavy constant gamma 3 ( AA505445 Hs 300697 66 724839 450923 ESTs AW043951 Hs 38449 66 42038063 454390 KIAA0906 protein AB020713 Hs 56966 66 449744988304 409632 serine (or cysteine) proteinase inhibit W74001 Hs 55279 66 3705067 409698 short stature homeobox 2 AF022654 Hs 55967 66 3783795074 410422 Homo sapiens, clone MGC 15203, mRNA co AL042014 Hs 63348 4625136 416078 protein tyrosine phosphatase, receptor AL034349 Hs 79005 9705538 417632 glycoprotein M6B R20855 Hs 379090 66 11415667 447499 protocadhenn beta 16 AW262580 Hs 147674 66 39347842 430200 geminin BE613337 Hs 234896 65 26586777 441094 MYC-associated zinc finger protein (pur U33819 Hs 7647 65 349734987473 420197 ESTs, Weakly similar to A57291 cytokine AW139647 Hs 88134 65 14295889 409731 thymosin, beta, identified in neuroblas AA125985 Hs 56145 65 3865080 452046 KIAA0802 protein AB018345 Hs 27657 65 427542768120 448672 ESTs AI955511 Hs 89582 65 40257917 445084 hypothetical protein FLJ14761 H38914 Hs 250848 65 37427687 408562 roundabout (axon guidance receptor, Dro AI436323 Hs 31141 65 2404971 414438 thioredoxm AI879277 Hs 76136 65 8165420 420568 protocadhenn alpha 10 F09247 Hs 247735 65 14625913 452017 prostate cancer associated protein 7 AF109302 Hs 27495 65 42708117 416820 glucose 6 phosphate dehydrogenase NM_000402 Hs 80206 64 1035 10365587 441020 ESTs W79283 Hs 35962 64 3495 7471 410361 guanylate binding protein 1 , interferon BE391804 Hs 62661 64 456 5132 435025 anchor attachment protein 1 (Gaalp, yea T08990 Hs 4742 64 3098 7117 410102 ESTs, homologue of PEM-3 [Ciona savigny AW248508 Hs 279727 64 422 5107 431204 cytochrome c oxidase subunit Via polype F28841 Hs 250760 64 2760 6848 448390 hypothetical protein AL035414 Hs 21068 64 3999 7897 411102 tπadin AA401295 Hs 23926 6 644 515 5175 420028 carbohydrate (N-acetylglucosamιne-6-O) AB014680 Hs 8786 6644 1408 14095872 434149 hypothetical protein MGC5469 Z43829 Hs 244624 6644 3030 7063 447733 MAD2 (mitotic arrest deficient, yeast, AF157482 Hs 19400 6644 3955 39567860 423605 cadhenn 19, type 2 AF047826 Hs 129887 6644 1826 18276179 446342 solute carrier family 7 (cationic ammo BE298665 Hs 14846 6644 3836 7762 405516 ENSP00000200457* Thyroid receptor inter 0644 4785 430681 ESTs AW969675 Hs 291232 6644 2719 6819 420005 ESTs AW271106 Hs 133294 6633 1407 5871 448595 KIAA0644 gene product AB014544 Hs 21572 6633 401540167910 414085 aldehyde dehydrogenase 1 family, member AA114016 Hs 75746 63 775 5384 417933 thymidylate synthetase X02308 Hs 82962 63 1170 1171 5692 414482 endothelm receptor type A S57498 Hs 76252 63 8248255426 453023 serine protease inhibitor, Kunitz type, AW028733 Hs 31439 63 4380 8208 423232 leucine-πch neuronal protein BE244625 Hs 125742 63 1787 6149 451763 hypothetical protein FLJ14220 AW294647 Hs 233634 63 4254 8103 412182 Splicing factor, arginine/seπne-rich, AA205588 Hs 73737 63 577 5226 452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 63 43104311 8150 438203 ESTs BE540090 Hs 7345 63 3308 7300 444329 hypothetical protein FLJ12921 W73753 Hs 209637 63 3693 7648 404030 NM_015669* Homo sapiens protocadhenn b 63 4735 431183 KDEL (Lys-Asp Glu-Leu) endoplasmιc retι M 006855 Hs 250696 63 275627576845 428450 KIAA0175 gene product NM 014791 Hs 1 84339 63 244324446621 400297 hypothetical protein DKFZp56401278 AI127076 Hs 288381 63 74618 452732 Homo sapiens, clone IMAGE 3535294, mRNA BE300078 Hs 80449 63 43488180 426053 poly(A)-bιndιng protein, cytoplasmic 1 U68105 Hs 172182 63 21636412 412507 EphA4 L36645 Hs 73964 63 5965975243 442117 ESTs, hypothetical protein for IMAGE 44 AW664964 Hs 128899 63 35517523 443247 c-Myc target JP01 BE614387 Hs 333893 63 3611 7578 422511 collagen, type XVII, alpha 1 AU076442 Hs 117938 63 16926078 429612 pituitary tumor-transforming 1 AF062649 Hs 252587 63 258625876726 446334 polymerase (RNA) II (DNA directed) poly U52427 Hs 75069 62 383438357761 431567 Homo sapiens cDNA FLJ21410 fis, clone N51357 Hs 260855 62 27996878 450785 Homo sapiens, alpha-1 (VI) collagen AA852713 Hs 108885 62 41938056 424263 L1 cell adhesion molecule (hydrocephalu M77640 Hs 1 57 6 2 192519266246 450835 hypothetical protein FLJ10767 BE262773 Hs 25584 62 41998060 421295 DC2 protein AW081061 Hs 103180 62 15245960 453883 cofactor required for Sp1 transcπption AI638516 Hs 347524 62 44598273 442432 hypothetical protein FLJ23468 BE093589 Hs 38178 6 1 35637535 422684 H2A histone family, member Z BE561617 Hs 119192 6 1 17266105 419833 Homo sapiens tryptophanyl-tRNA syntheta AA251131 Hs 220697 6 1 13885856 453331 ESTs AI240665 Hs 352537 6 1 44138236 432693 ESTs AW449630 Hs 293790 6 1 29006958 414591 ESTs, Weakly similarto ALU8_HUMAN ALU AI888490 Hs 248107 6 1 8345435 400263 Eos Control Hs 75309 6 1 4613 438915 Williams-Beuren syndrome chromosome reg AA280174 Hs 355711 6 1 33657348 406672 major histocompatibility complex, class M26041 Hs 198253 6 1 43444820 435099 flap structure specific endonuclease 1 AC004770 Hs 4756 61 310431057123 422100 ADP-nbosylation factor-like 7 AI096988 Hs 111554 6 1 16446042 415702 gb HSPD18414 HM3 Homo sapiens cDNA don F28877 Hs 73680 6 1 9425515 408901 hypothetical protein FLJ10468 AK001330 Hs 48855 6 1 2722734997 402810 NM-.004930* Homo sapiens capping protein 6 1 4692 421335 ARS component B X99977 Hs 103505 6 1 152915305964 425272 ESTs, Weakly similar to C35826 hypothet AA354138 Hs 47209 6 1 20786355 438944 KIAA1444 protein AA302517 Hs 92732 6 1 33687351 430044 ESTs AA464510 Hs 152812 6 1 26426765 416640 neuron-specific protein BE262478 Hs 13406 6 1 10195576 424440 ESTs AA340743 Hs 133208 6 1 1951 6266 403857 Target Exon 6 1 4730 406836 immunoglobulin kappa constant AW514501 Hs 156110 6 0 684835 421878 Homo sapiens cDNA FLJ11643 fis, clone H AA299652 Hs 111496 60 16076017 419452 PTK7 protein tyrosine kinase 7 U33635 Hs 90572 60 134013415821 407688 Human D9 splice variant B mRNA, complet W25317 Hs 37616 60 1494894 430686 desmoglem 1 NMJ01942 Hs 2633 60 272127226821 427375 metallocarboxypeptidase CPX-1 AL035460 Hs 177536 60 232023216522 451698 endothelm converting enzyme like 1 Y16187 Hs 26880 60 424942508100 419956 cadhenn 19, type 2 AL137939 Hs 40096 60 13985865 430439 DKFZP434B061 protein AL133561 Hs 380155 60 269526966803 425292 37 kDa leucine rich repeat (LRR) protei NM_005824 Hs 1 55545 60 208320846359 400244 Eos Control Hs 7957 60 4606 407788 SlOO calcium-bindmg protein A2 BE514982 Hs 38991 60 1614905 406663 immunoglobulin heavy constant mu U24683 60 39404818 429903 cyclin dependent kinase 5, regulatory s AL134197 Hs 93597 60 26166746 426158 v-erb b2 avian erythroblastic leukemia NMJ01982 Hs 1 99067 60 218421856428 408829 heparan sulfate (glucosamine) 3-0 sulfo NM_006042 Hs 48384 60 2642654991 424326 ADAM like disintegnn protease, decysin NMJ14479 Hs 1 45296 60 193419356252 410240 synaptojanm 2 AL157424 Hs 61289 60 4375117 408938 ESTs AA059013 Hs 22607 60 2795002 409028 Z-band alternatively spliced PDZ motif AB014513 Hs 49998 60 2962975015 411372 low density lipoprotem receptor (famil AI147861 Hs 213289 60 5305188 420303 KIAA1474 protein AA258282 Hs 278436 60 14435900 407844 ESTs AW073716 Hs 8037 60 1684912 431448 hypothetical protein DKFZp56401278 AL137517 Hs 306201 60 278527866869 415701 gamma glutamyl hydrolase (conjugase, fo NM 003878 Hs 78619 60 9409415514 428834 ESTs AW899713 Hs 10338 60 24796647 425930 nbosomal protein L18a H93691 Hs 163593 60 21546406 421506 thymidine kinase 1, soluble BE302796 Hs 105097 60 15505976 451149 RNA binding motif protein 8B AL047586 Hs 10283 59 42148073 448493 ESTs AI524124 Hs 270307 59 40067903 437330 Homo sapiens mRNA, cDNA DKFZp761J1112 ( AL353944 Hs 50115 59 32537250 416297 solute carrier family 25 (mitochoπdπal AA157634 Hs 79172 59 9885553 424049 KIAA0624 protein AB014524 Hs 138380 59 188918906222 433124 hypothetical protein SMAP31 U51712 Hs 13775 59 29426992 422809 hypothetical protein FLJ10549 AK001379 Hs 121028 59 174117426115 414522 Immunoglobulin J chain AW518944 Hs 76325 59 8275428 451598 ESTs N29102 Hs 79658 59 42418093 414732 minichromosome maintenance deficient (SAW410976 Hs 77152 59 8595453 408122 hypothetical protein FLJ10718 AI432652 Hs 42824 59 1934935 433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 59 292329246977 414763 quiescm Q6 U97276 Hs 77266 59 8668675459 434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 59 30577083 418394 Kruppel like factor 5 (intestinal) AF132818 Hs 84728 59 123012315737 417891 protein phosphatase 1, regulatory (inhi W79410 Hs 82887 59 11645687 434203 hypothetical protein PR01855 BE262677 Hs 283558 59 30337066 443780 activating transcription factor 5 NM 012068 Hs 9754 59 364336447606 439963 platelet-activating factor acetylhydrol AW247529 Hs 6793 59 34417423 431243 syπdecan 4 (amphiglycaπ, ryudocan) U46455 Hs 252189 59 27676854 427400 hypothetical protein FLJ11939 AW245084 Hs 94229 59 23256525 429207 ESTs AA447941 Hs 123423 59 25326686 417675 similar to murine leucine-πch repeat p AI808607 Hs 3781 59 11445670 410929 ESTs H47233 Hs 30643 58 5045166 408716 Homo sapiens mRNA for KIAA1769 protein, AI567839 Hs 151714 58 2514981 432691 mitogen activated protein kinase 7 U29725 Hs 3080 58 289728986956 432247 ESTs AA531287 Hs 105805 58 28596923 434629 glioma-amplified sequence 41 AA789081 Hs 4029 58 30647090 431070 transcription factor 19 (SC1) AW408164 Hs 249l84 58 27446837 426991 Homo sapiens cDNA FLJ 10674 fis, clone N AK001536 Hs 214410 58 22946502 436895 carbonic anhydrase XII AF037335 Hs 5338 58 322432257224 413313 glycyl-tRNA synthetase NMJ02047 Hs 293885 58 6997005325 428342 Homo sapiens CDNA FLJ13458 fis, clone P AI739168 Hs 349283 58 24326611 424441 H2A histone family, member X X14850 Hs 147097 58 195219536267 445930 Homo sapiens clone 24747 mRNA sequence AF055009 Hs 13456 58 38047734 402260 NM-.001436* Homo sapiens fibπllann (FB 58 4676 422386 heparaπ sulfate (glucosamme) 3 O-sulfo AF105374 Hs 115830 58 167616776067 406621 immunoglobulin lambda locus X57809 Hs 181125 58 26274810 414638 stress-associated endoplasmic reticulum W03516 Hs 76698 58 8405440 437597 SCG10 like protein AA730767 Hs 285753 58 32737267 418110 hypothetical protein FLJ22202 R43523 Hs 217754 58 11935710 422268 maternal G10 transcnpt N25485 Hs 330310 58 16676060 413566 sprouty (Drosophila) homolog 4 AW604451 Hs 381153 58 7305347 414695 proteasome (prosome, macropain) subunit BE439915 Hs 76913 58 8505446 415200 SWI/SNF related, matπx associated, act AL040328 Hs 78202 58 9205496 422627 transforming growth factor, beta-induce BE336857 Hs 118787 58 17156097 415672 ESTs N53097 Hs 193579 58 9375511 419437 neogemn (chicken) homolog 1 U61262 Hs 90408 58 133813395820 420531 ribosome binding protein 1 (dog 180kD h AI652069 Hs 98614 58 14595911 433058 Homo sapiens, Similar to CG8405 gene pr H86865 Hs 380962 57 29336985 430285 ESTs AI917602 Hs 106440 57 26756789 400252 NM_004651* Homo sapiens ubiquitm speci Hs 171501 57 4609 409637 Homo sapiens mRNA, cDNA DKFZp434K0621 ( AA323948 Hs 55407 57 3725069 445515 Homo sapiens, clone IMAGE 3457003, mRNA BE388665 Hs 1 9999 57 37767713 450847 stanniocalcin 1 NMJ03155 Hs 25590 57 420142028062 415444 solute carrier family 20 (phosphate tra BE247295 Hs 78452 57 9265502 425863 Human unidentified mRNA, partial sequen U43604 Hs 159901 57 21526404 448386 KIAA1329 protein AB037750 Hs 21061 57 399739987896 408482 adenosine A2b receptor NMJ00676 Hs 45743 57 2262274959 429921 collagen, type XI, alpha 1 AA526911 Hs 82772 57 26206749 426968 amphiphysin (Stiff-Mann syndrome with b U07616 Hs 173034 57 229022916499 440516 cadhenn 2, type 1, N cadhenn (neurona S42303 Hs 161 57 347234737451 444783 anilliπ (Drosophila Scraps homolog), ac AK001468 Hs 62180 57 372237237672 424223 putative DNA/chromatm binding motif AJ243706 Hs 143323 57 191519166240 450087 MUM2 protein BE293180 Hs 24379 57 41338008 427550 nuclear RNA helicase, DECD variant of D BE242818 Hs 311609 57 23426538 428977 cyclin B2 AK001404 Hs 194698 57 24966659 428171 nbosomal protein L35 AA489323 Hs 182825 57 24026587 422311 cytokine receptor-like factor 1 AF073515 Hs 114948 57 166916706062 418533 myosin binding protein C fast-type NMJ04533 Hs 85937 57 125312545754 436396 wingless type MMTV integration site fam AI683487 Hs 152213 57 31847189 431457 integrin, alpha 11 NMJ12211 Hs 256297 57 278727886870 417920 adenosine monophosphate deammase 2 (is S47833 Hs 82927 57 116711685690 428520 hypothetical protein FLJ10097 AA331901 Hs 184736 57 24526626 441544 ESTs AW300043 Hs 127137 57 35237496 429002 junction plakoglobm AW248439 Hs2340 56 24986661 420190 hypothetical protein EST00098 AI816209 Hs 95867 56 14285888 419745 slug (chicken homolog), zincfingerpro AFO420O1 Hs 93005 56 138113825851 419517 Homo sapiens clone 23620 mRNA sequence AF052107 Hs 90797 56 13465825 419073 transmembrane receptor Unc5H2 mRNA AW372170 Hs 183918 56 12965786 425071 deiod ase, lodothyronine, type II NMJ13989 Hs 1 54424 56 204320446330 407366 gb Homo sapiens cιg33 mRNA, partial seq AF026942 Hs 17518 56 1374885 428862 SRY (sex determining region Y)-box 9 (c NM_000346 Hs 2316 56 248324846650 430281 CGI-69 protein AI878842 Hs 237924 56 26746788 437188 KIAA1814 protein AL080221 Hs 375566 56 32407238 442549 TNF receptor-associated factor 4 AI751601 Hs 8375 56 35677538 413076 weel (S pombe) homolog U10564 Hs 75188 56 6786795310 442700 hypothetical protein MGC5576 AA377618 Hs 103834 56 35787548 408958 signal recognition particle 54kD T99607 Hs 49346 56 2835005 457458 ESTs AW972881 Hs 276507 56 45528352 416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 56 100110025564 432559 ESTs AW452948 Hs 257631 56 28866947 453582 hypothetical protein FLJ11937 AW854339 Hs 33476 56 44278247 445363 tubulm specific chaperone d NMJ05993 Hs 12570 56 376237637702 447343 ESTs, Highly similar to S02392 alpha-2- AA256641 Hs 236894 56 39167828 427498 methyl-CpG binding domain protein 3 NM 003926 Hs 178728 56 233623376534 433212 ESTs BE218049 Hs 121820 56 29567001 414561 Homo sapiens ammo acid transport syste AI064813 Hs 195155 56 8315432 407103 hypothetical protein MGC13170 AA424881 Hs 256301 56 1104862 428976 ras homolog gene family, member I AL037824 Hs 194695 56 24956658 440848 ATPase, H transporting, lysosomal (vacu BE314650 Hs7476 56 34887464 427052 CK2 interacting protein 1 , HQ0024c prot AF168676 Hs 173380 55 229822996506 405058 Target Exon 55 4769 428028 ιnterleukιn-1 receptor-associated kmas U52112 Hs 182018 55 23926578 447712 kinesm family member C3 BE622873 Hs23131 55 39517857 420842 hypothetical protein MGC10986 AI083668 Hs 50601 55 14855929 411789 Adlican AF245505 Hs72157 55 5535545207 410581 tumor endothelial marker 7/precursor AA018982 Hs 125036 55 4785146 420376 protocadhenn 18 AL137471 Hs 97266 55 144714485903 418336 glutathioπe peroxidase 3 (plasma) BE179882 Hs 353196 55 12195730 424688 myosin, light polypeptide 3, alkali ve AA216287 Hs1815 55 19886290 424481 proteolipid protein 1 (Pelizaeus-Merzba R19453 Hs 1787 55 19606272 411021 titin F00055 Hs 172004 55 5085169 432994 ESTs AA573452 Hs 150941 55 29226976 418004 aldehyde dehydrogenase 3 family, member U37519 Hs 87539 55 117411755695 438937 ESTs AW952654 Hs73964 55 33677350 413199 ELAV (embryonic lethal, abnormal vision M62843 Hs 75236 55 6876885317 432406 KIAA0969 protein AI340571 Hs 343666 55 28716933 425262 GS3955 protein D87119 Hs 155418 55 207620776354 454071 ESTs AI041793 Hs42502 55 44878295 422515 multifunctional polypeptide similar to AW500470 Hs 117950 55 16936079 452281 Homo sapiens cDNA FLJ 11041 fis, clone P T93500 Hs 28792 55 43098149 418526 solute carrier family 16 (monocarboxyli BE019020 Hs 85838 55 1251 5752 434078 chromosome 8 open reading frame 4 AW880709 Hs 283683 55 30277060 428748 Ksp37 protein AW593206 Hs 98785 55 24686638 422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 55 17346110 423915 alpha actιnιn-2-assocιated LIM protein AF039018 Hs 135281 55 186918706209 428291 interferon stimulated gene (20kD) AA534009 Hs 183487 55 24236604 439999 ras homolog gene family, member E AA115811 Hs 6838 55 34447426 419488 nucleophosmin/πucleoplasmm 3 AA316241 Hs 90691 55 13425822 439688 hypothetical protein FLJ12921 AW445181 Hs 209637 55 34187401 434175 ESTs AW979081 Hs 165469 55 30327065 429441 lipophilm B (uteroglobm family member AJ224172 Hs 204096 55 256025616708 443572 cleavage and polyadenylation specific f AA025610 Hs9605 55 36257589 424078 paternally expressed 3 AB006625 Hs 139033 55 189318946225 450998 splicing factor 3b, subunit 4, 49kD BE387614 Hs 25797 54 42058065 400259 NMJ17432* Homo sapiens prostate tumor Hs 19555 54 4610 407785 ESTs, Weakly similar to A43932 mucm 2 AW207285 Hs98279 54 1604904 435854 putative ankyπn-repeat containing prot AJ278120 Hs 4996 54 315731587166 457211 ESTs, Weakly similar to S51797 vasodila AW972565 Hs 32399 54 45438344 419682 paired like homeodomam transcription f H13139 Hs 92282 54 13685841 407178 AP-2 beta transcription factor AA195651 Hs 352312 54 1184870 416065 proliferating cell nuclear antigen BE267931 Hs78996 54 9685536 418532 neurotrophic tyrosine kinase, receptor, F00797 Hs 374321 54 12525753 427337 Fc fragment of IgG low affinity lllb, Z46223 Hs 176663 54 231823196521 448517 hypothetical protein FLJ22649 similar t AA082750 Hs42194 54 40097906 452401 tumor necrosis factor, alpha induced pr NMJ07115 Hs 29352 54 432543268161 450414 KIAA1716 protein AI907735 Hs 21446 54 41658033 445932 Homo sapiens clone 24859 mRNA sequence BE046441 Hs 333555 54 38057735 427923 FGENESH predicted 11 TM protein AW274357 Hs 301406 54 23856572 430130 Homo sapiens mRNA, cDNA DKFZp761G02121 AL137311 Hs 23407454 265026516772 428121 KIAA0284 protein AB006622 Hs 182536 54 239823996584 408660 ESTs, Moderately similar to PC4259 ferr AA525775 Hs 89040 54 2474977 410011 PFTAIRE protein kinase 1 AB020641 Hs 57856 54 4064075096 425616 nuclear matrix protein NMP200 related t BE561911 Hs 173980 54 2121 6384 442578 hypothetical protein FLJ10781 AK001643 Hs 8395 54 357235737543 414751 choline kinase AL120829 Hs 77221 54 8635456 437763 tissue inhibitor of metalloproteinase 1 AA469369 Hs 5831 54 32857278 427674 H2B histone family, member Q NM_003528 Hs 2 178 54 235923606553 404458 CX000877* gι| 11877268|emb|CAC18893 1| ( 54 4749 450296 hepatocyte growth factor-regulated tyro AL041949 Hs 24756 54 41538023 419236 Homo sapiens cDNA FLJ 11481 fis, clone H AA330447 Hs 135159 53 1321 5805 435256 cytokine-like protein C17 AF193766 Hs 13872 53 311631177133 447436 Homo sapiens cDNA FLJ21449 fis, clone AI932971 Hs 18593 53 39287837 400235 NM_005336:Homo sapiens high density lip Hs.177516 5.3 4604 435593 DKFZP586J1624 protein R88872 Hs.4964 5.3 31417153 441362 RAD51 (S. cerevisiae) homolog (E coli R BE614410 Hs.23044 5.3 35127486 424971 tumor suppressing subtransferable candi AA479005 Hs.154036 5.3 20356324 426514 bone morphogenetic protein 7 (osteogeni BE616633 Hs.170195 5.3 22466470 451681 ESTs, Weakly similar to AA64_HUMAN 64 K Z28564 Hs.255950 5.3 42458097 445302 hypothetical protein FLJ10675 AK001537 Hs.12488 5.3 375737587699 432504 oxygen regulated protein (150kD) AL121015 Hs.277704 5.3 28796941 413762 FK506-binding protein 4 (59kD) AW411479 Hs.848 5.3 7385354 453905 LIM domain kinase 1 NM_002314 Hs.3 6566 5.3 446244638276 419693 FXYD domain-containing ion transport re AA133749 Hs.301350 5.3 13715844 421778 actin related protein 2/3 complex, subu AA428000 Hs.283072 5.3 1591 6003 449129 ESTs AI631602 Hs.258949 5.3 40667950 432647 fibroblast growth factor receptor 2 (ba AI807481 Hs.278581 5.3 28946953 406830 peptidylprolyl isomerase A (cyclophilin AI829848 Hs.342389 5.3 674834 452410 Homo sapiens mRNA; cDNA DKFZp434E2321 ( AL133619 Hs.29383 5.3 432843298163 418045 ESTs AI972919 Hs.118837 5 5..33 11835701 430326 DKFZP727I051 protein BE251590 Hs.239370 5.3 26796793 419088 integrin, beta 8 AI538323 Hs.380684 5.3 13035791 416860 actin filament associated protein D25248 Hs.80306 5.3 10435593 456181 ras inhibitor L36463 Hs.1030 5.3 451645178321 430838 hypothetical protein FLJ12015 N46664 Hs.169395 5.3 27336829 439053 chaperonin containing TCP1 , subunit 2 ( BE244588 Hs.6456 5.3 33747357 444354 hypothetical protein R33729 AA847582 Hs.10927 5.3 36947649 421846 protein kinase C substrate 80K-H AA017707 Hs.1432 5.3 1601 6012 425703 collagen, type VI, alpha 2 X06195 Hs.159263 5.3 212621276387 433180 K562 cell-derived leucine-zipper-like p AB038651 Hs.31854 5.3 294929506997 408826 Homo sapiens clone HB-2 mRNA sequence AF216077 Hs.48376 5.3 2634990 428227 small inducible cytokine subfamily B (C AA321649 Hs.2248 5.3 24106593 431565 butyrate-induced transcript 1 AF161470 Hs.260622 5.3 279527966876 422363 replication factor C (activator 1) 3 (3 T55979 Hs.115474 5.3 16736065 418870 chemokine (C-X-C motif), receptor 4 (fu AF147204 Hs.89414 5.3 127912805773 417089 Homo sapiens cDNA: FLJ21909 fis, clone H52280 Hs.18612 5.3 10775619 406885 gb:Human mRNA for pre-mRNA splicing fac D28423 5.3 73744840 446157 Homo sapiens cDNA: FLJ22562 fis, clone BE270828 Hs.131740 5.3 3821 7749 404208 O5001282:gi|4504223|ref|NP )00172.1| gl 5.3 4740 404854 Target Exon 5.3 4762 445875 Homo sapiens clone 24453 mRNA sequence AF070524 Hs.13410 5.3 3801 7731 448603 DNA segment on chromosome X and Y (uniq L03426 Hs.21595 5.3 401740187911 417079 interleukin 1 receptor antagonist U65590 Hs.81134 5.3 107310745616 438393 Homo sapiens cDNA: FLJ22272 fis, clone AA351815 Hs.50740 5.3 33197309 426613 hydroxyacyl-Coenzyme A dehydrogenase, t U96132 Hs.171280 5.3 225722586476 412564 cardiac ankyrin repeat protein X83703 Hs.355934 5.3 6066075251 441389 endocytic receptor (macrophage mannose AF134838 Hs.7835 5.3 351435157488 403171 C2001472*;gi|5809678Igb|AAB41848.2| (U6 5.2 4710 410223 calsequestrin 1 (fast-twitch, skeletal S73775 Hs.60708 5.2 4334345115 425848 valyl-tRNA synthetase 2 BE242709 Hs.159637 5.2 21506402 415697 DKFZP566I1024 protein AI365603 Hs.279696 5.2 9395513 449644 ESTs AW960707 Hs.8935 5.2 41047984 447519 ESTs U46258 Hs.339665 5.2 39367844 421920 gamma-aminobutyric acid (GABA) receptor BE551245 Hs.1438 5.2 16146022 435060 ESTs, Weakly similar to fork head like AI422719 Hs.120873 5.2 31017120 449139 phenylalanine-tRNA synthetase-like BE268315 Hs.23111 5.2 40677951 428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs.337534 5.2 23936579 414267 dimelhylargiπine dimethylaminohydrolase AL078459 Hs.303180 5.2 7955402 424291 ephrin-B1 AL120051 Hs.144700 5.2 19316249 425712 ESTs, Moderately similar to ALU1_HUMAN AA412548 Hs.21423 5.2 21306389 419285 KIAA0062 protein D31887 Hs.89868 5.2 132513265809 406636 gb:Homo sapiens (clone WR4.12VL) anti-t L12064 5.2 32334814 408212 hypothetical protein AA297567 Hs.43728 5.2 2064945 433320 ESTs, Highly similar to CTXN RAT CORTEX D60647 Hs.250879 5.2 29697010 440700 guanine nucleotide binding protein (G p AW952281 Hs.296184 5.2 34817458 402855 NM_001839*:Homo sapiens calponin 3, aci 5.2 4694 414175 hypothetical protein DKFZp761D112 AI308876 Hs.103849 5.2 7865394 413815 discoidin domain receptor family, membe AL046341 Hs.75562 5.2 7455360 428865 BarH-like homeobox 1 BE544095 Hs.164960 5.2 24856651 450701 hypothetical protein XP 098151 (leucine H39960 Hs.288467 5.2 41838048 424442 ESTs, Weakly similar to ZN91_HUMAN ZINC AW051949 Hs.90035 5.2 19546268 450680 Homo sapiens clone 25194 mRNA sequence AF131784 Hs.25318 5.2 4181 8046 438619 TU12B1-TY protein AB032773 Hs.374350 5.2 334033417327 428727 general transcription factor IIH, polyp AF078847 Hs.78452 5.2 246624676637 422175 ESTs, Highly similar to T00391 hypothet N79885 Hs.6382 5.2 16576053 408604 ESTs D51408 Hs.21925 5.1 2434973 404815 ENSP00000251989*:DJ100N22.1 (NOVEL EGF- 5.1 4761 416700 cathepsin D (lysosomal aspartyl proteas AW498958 Hs.343475 5.1 10235579 442285 uncharacterized hypothalamus protein HT W28729 Hs.374989 5.1 35547526 430333 TIA1 cytotoxic granule-associated RNA-b S70114 Hs.239489 5.1 268026816794 433882 procollagen-proline, 2-oxoglutarate 4-d U90441 Hs.3622 5.1 301230137047 415705 coilin U06632 Hs.966 5.1 9439445516 450983 ER01 (S. cerevisiae)-like AA305384 Hs.25740 5.1 42048064 426138 Homo sapiens clone 23798 and 23825 mRNA D81871 Hs.167036 5.1 21786423 418607 KIAA1402 protein AL137426 Hs.86392 5.1 12605759 421857 hypothetical protein FLJ23322 AW601852 Hs.285932 5.1 16046014 424375 Homo sapiens clone 24820 mRNA sequence AF070547 Hs.146312 19396256 449475 hypothetical protein PP1057 AI348027 Hs.129826 40917973 408196 SRY (sex determining region Y)-box 22 AL034548 Hs.43627 1992004940 437044 differentially expressed in Fancom's a AL035864 Hs 69517 5 1 3233 7232 436291 protein regulator of cytokinesis 1 BE568452 Hs 344037 5 1 3180 7185 429150 smoothened (Drosophila) homolog AF120103 Hs 197366 5 1 251925206677 441954 Fanconi anemia, complementation group G AI744935 Hs 8047 5 1 3542 7514 414465 nbosomal protein S5 AW270645 Hs 76194 51 820 5423 421140 signal sequence receptor, delta (transl AA298741 Hs 102135 5 1 1509 5948 432731 fibronectin 1 R31178 Hs 287820 5 1 2904 6961 427157 thymme-DNA glycosylase U51166 Hs 173824 5 1 23052306 6511 437191 seπne protease inhibitor, Kazal type, NMJ06846 Hs 331555 5 1 3241 32427239 442173 KIAA0144 gene product N76101 Hs 8127 51 3552 7524 418059 gb zn56d05 s1 Stratagene muscle 937209 AA211586 5 1 1186 5703 424005 vang (van gogh, Drosophιla)-lιke 2 AB033041 Hs 137507 5 1 1883 18846218 434669 core histone macraH2A22 AF151534 Hs 92023 51 306830697093 433819 ESTs AW511097 Hs 110069 5 1 3007 7042 435056 glycoprotein M6B AW023337 Hs 5422 5 1 3100 7119 431205 tropomodulm 4 (muscle) AA194560 Hs 250763 5 1 2761 6849 418867 msh (Drosophila) homeo box homolog 2 D31771 Hs 89404 51 1277 12785772 406851 major histocompatibility complex, class AA609784 Hs 352392 5 1 71 4838 410687 lysyl oxidase-like 1 U24389 Hs 65436 5 1 4854865153 412490 Homo sapiens cDNA FLJ22528 fis, clone AW803564 Hs 288850 5 1 595 5242 408056 ephrιn-A4 AA312329 Hs 42331 5 1 188 4930 412446 ESTs AI768015 Hs 352375 51 586 5235 432370 N-acetylneuraminic acid phosphate synth AA308334 Hs 274424 5 1 2867 6930 448140 BCM-like membrane protein precursor AF146761 Hs 20450 5 1 39803981 7882 427584 v-myb avian myeloblastosis viral oncoge BE410293 Hs 179718 5 1 2348 6542 442061 abl-interactor 12 (SH3-contaιnιng prate AA774284 Hs 285728 5 1 3547 7519 417709 KIAA0247 gene product D87434 Hs 82426 51 114911505674 444019 putative nucleolar RNA helicase BE173977 Hs 10098 5 1 3670 7629 433012 ATX1 (antioxidant protein 1, yeast) hom NM_004045 Hs 279910 51 292529266978 449353 ESTs AA001220 Hs 242947 5 1 4084 7966 438866 tissue inhibitor of metalloproteinase 2 U44385 Hs 6441 5 1 33603361 7344 434355 ESTs AA630865 Hs 186556 5 1 3049 7076 417796 ESTs AA206141 Hs 367818 5 1 1159 5682 410279 hypothetical protein FU14117 BE271977 Hs 61809 51 447 5124 440028 ESTs, Weakly similar to T17227 hypothet AW473675 Hs 367649 5 1 3446 7428 407241 gb Human omega light chain protein 141 M34516 5 1 130 131 4880 421566 early growth response 2 (Krox-20 (Droso NMJ00399 Hs 1 395 5 1 1563 15645984 400220 Eos Control Hs 155560 50 4600 448425 ESTs AI500359 Hs 371249 50 40047901 428013 hypothetical protein AF151020 Hs 181444 50 239023916577 405387 NM_022170* Homo sapiens Williams-Beuren 50 4779 439070 ESTs AI733278 Hs 7621 50 33757358 436543 integπn beta 4 binding protein NMJ02212 Hs 5215 50 319831997201 450065 transcriptional co-activator with PDZ b AL050107 Hs 24341 50 413041318006 433043 lymphoid nuclear protein (LAF-4) mRNA W57554 Hs 125019 50 29306982 417166 Paired box protein Pax-3 AA431323 Hs 42146 50 10885628 444984 fatty acid desaturase 1 H15474 Hs 132898 50 37377683 422066 maiate dehydrogenase 2, NAD (mitochondr AW249275 Hs 343521 50 16346036 417437 interferon regulatory factor 4 U52682 Hs 82132 50 112311245656 403081 NM_003319* Homo sapiens titin (TTN), mR 50 4704 439453 thyroid hormone receptor mteractor 13 BE264974 Hs 6566 50 33997382 425322 protein kinase, DNA-activated, catalyti U63630 Hs 155637 50 208920906363 434837 lysophosphatidic acid acyltransferase-d AF156776 Hs 353175 50 308030817102 414420 immediate early response 3 AA043424 Hs 76095 50 8145418 400300 HER2 receptor tyrosine kinase (c erb b2 X03363 Hs 323910 50 894619 447898 6 2 kd protein AW969638 Hs 380920 50 39667868 412819 FK506 binding protein precursor T25829 Hs 24048 50 6515286 452110 Homo sapiens cDNA FLJ11309 fis, clone P T47667 Hs 28005 50 42908132 432211 hypothetical protein FLJ10986 BE274530 Hs 273333 50 28526917 457060 beta tubul l, class VI AA402364 Hs 303023 50 45388339 430152 aquaponn 3 AB001325 Hs 234642 50 265326546774 409299 small nuclear πbonucleoprotein D2 poly AA045650 Hs 53125 50 3395045 443802 KIAA1291 protein AW504924 Hs 9805 50 36477609 445162 piccolo (presynaptic cytomatnx protein AB011131 Hs 12376 50 374937507693 417115 small nuclear πbonu eoprotein polypep AW952792 Hs 334612 50 10815622 409944 four and a half LIM domains 3 BE297925 Hs 57687 50 3995090 416801 sal (Drθ5ophιla)-lιke 2 X98834 Hs 79971 5 0 10325585 445160 sine oculis homeobox (Drosophila) homol AI299144 Hs 101937 50 37487692 429139 ESTs F09092 Hs 66087 50 25176675 445462 hypothetical protein MGC3077 AA378776 Hs 288649 50 37717709
TABLE 8B
Pkey Unique Eos probeset identifier number CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession 406782 0J AA430373 AA968771 406636 0_0 L12064 L12083 L12065 L12075 L12066 L12085 L12072 L12082 L12081 L12062 L12080 418059 1164438 AA211586 F35799 F29720 AW937408 AW937387 AA211641
TABLE 8C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers 'Dunham I et al " refers to the publication entitled The DNA sequence ofhuman chromosome 22 " Dunham l et al , Nature (1999) 402489-495
Strand Indicates DNA strand from which exons were predicted
NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
405001 6015406 Minus 104646-104819
404977 3738341 Minus 43081-43229
401781 7249190 Minus 83215 83435,83531-83656,83740 83901,8423
405443 7408143 Plus 90716-90887,101420-101577
403088 8954241 Plus 169894-170193,170504-170806
402992 7767907 Minus 42137-42515
401780 7249190 Minus 28397-28617,28920-29045,29135-29296,2941
401673 7689903 Minus 122587-122705,122765-123047
401797 6730720 Plus 6973-7118
401566 8469090 Minus 96277-96420,96979-97160
400499 9796071 Minus 148495-148806
405516 9454624 Plus 112707-112876,113676-113854
404030 7671252 Plus 149362-151749
402810 6010110 Plus 12715-12856,13527-13643
403857 7708910 Minus 2524-3408
402260 3399665 Minus 113765-113910,115653-115765,116808-11694
405058 7655685 Plus 150740-151556
404458 7770571 Minus 35710-36276
404208 3080468 Minus 105346-105573
404854 7143420 Plus 14260-14537
403171 9838164 Minus 74502-74703
402855 9662953 Minus 59763-59909
404815 5911819 Minus 64494-64691
405387 6587915 Minus 3769-3833,5708 5895
403081 8954241 Plus 155749-156048,156142-156459
TABLE S
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of malignant fibrous histiocytoma AIs divided by the 50th percentile of normal body tissue AIs, where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search puφoses
Pkey Gene Name Accession UniGene RATIO SEQ ID#
426300 delta like homolog (Drosophila) U15979 Hs 169228 225 219621976437
404977 Insulin-like growth factor 2 (somatomed 21 4 4766
422487 mucm 4, tracheobronchial AJ010901 Hs 198267 199 1689 16906076
406687 matrix metalloproteinase 11 (stromelysi M31126 Hs 352054 183 49504823
418338 neuronal pentraxin I NM 002522 Hs 84154 165 1220 1221 5731
409633 ESTs AW449822 Hs 55200 164 371 5068
429359 matnx metalloproteinase 14 (membrane i W00482 Hs 2399 162 2551 6702
450701 hypothetical protein XP_098151 (leucine H39960 Hs 288467 158 4183 8048
425247 matnx metalloproteinase 11 (stromelysi NM 005940 Hs 1 55324 151 207220736351
444670 hypothetical protein MGC5370 H58373 Hs 332938 144 3714 7666
422867 cartilage oligomeric matrix protein (ps L32137 Hs 1584 136 1751 17526122
420162 cyclin dependent kinase 4 BE378432 Hs 95577 135 1422 5883
453857 Ras-mduced senescence 1 (RIS1) AL080235 Hs 35861 133 444944508266
422887 ESTs AI751848 Hs 49215 13 3 1755 6124
412709 KIAA0027 protein AL022327 Hs 74518 13 2 631 6325269
430044 ESTs AA464510 Hs 152812 130 2642 6765
408202 DKFZP586L151 protein AA227710 Hs 43658 127 202 4942
413554 secretograπin II (chromogranm C) AA319146 Hs 75426 126 729 5346
415166 carboxypeptidase Z NM 003652 Hs 78068 12 3 913 9145491
422386 heparan sulfate (glucosamine) 3 O-sulfo AF105374 Hs 115830 11 8 1676 16776067
424687 matrix metalloproteinase 9 (gelat ase J05070 Hs 151738 11 8 1986 19876289
444381 hypothetical protein BC014245 BE387335 Hs 283713 11 7 3697 7652
442426 hypothetical protein MGC5370 AI373062 Hs 332938 11 7 3562 7534
452620 ESTs AA436504 Hs 119286 11 5 4338 8172
446619 secreted phosphoprotein 1 (osteopontin, AU076643 Hs 313 11 5 3861 7782
418140 microfibπllar-associated protein 2 BE613836 Hs 83551 11 4 1196 5713
414477 amplified in osteosarcoma U41635 Hs 76228 11 4 822 8235425
423575 intron of peπostin (OSF-2os) C18863 Hs 163443 11 3 1820 6173
453331 ESTs AI240665 Hs 352537 11 3 4413 8236
422424 prostate differentiation factor AI186431 Hs 296638 11 2 1681 6070
418399 hypothetical protein FLJ12442 AF131781 Hs 84753 11 2 1232 1233 5738
425292 37 kDa leucine-nch repeat (LRR) protei NMJ05824 Hs 1 55545 11 2 208320846359
426559 paired basic ammo acid cleaving system AB001914 Hs 170414 11 2 2253 22546474
423961 peπostin (OSF-2os) D13666 Hs 136348 11 1 1878 18796215
409132 protein kinase, AMP-activated, beta 2 n AJ224538 Hs 50732 11 1 309 3105025
418054 lysyl oxidase like 2 NM 002318 Hs 83354 11 1 1184 11855702
421458 carbohydrate (keratan sulfate Gal 6) su NM 003654 Hs 1 04576 11 1 1543 15445972
452401 tumor necrosis factor, alpha induced pr NM 007115 Hs 29352 11 0 43254326 8161
415989 ESTs AI267700 Hs 351201 108 962 5530
439755 B7 homolog 3 AW748482 Hs 77873 108 3430 7413
419762 ESTs AI608647 Hs 32374 106 1387 5855
451934 ESTs AI540842 Hs 61082 105 4262 8109
428311 tryptophan 2,3-dιoxygenase NM 005651 Hs 1 83671 105 242924306609 417308 KIAA0101 gene product H60720 Hs 81892 104 1094 5634
442700 hypothetical protein MGC5576 AA377618 Hs 103834 10 2 3578 7548
404550 Target Exon 10 1 4750
437330 Homo sapiens mRNA, cDNA DKFZp761 J1112 ( AL353944 Hs 50115 100 3253 7250
442285 uncharacterized hypothalamus protein HT W28729 Hs 374989 100 3554 7526
413004 interleukin enhancer binding factor 2, T35901 Hs 75117 99 667 5300
434449 hypothetical protein FLJ22041 similar t AW953484 Hs 3849 99 3057 7083
423472 breast carcinoma amplified sequence 1 AF041260 Hs 129057 99 1812 18136167
426156 natπuretic peptide receptor A/guanylat BE244537 Hs 167382 99 2183 6427
419741 ubiquitm earner protein E2-C NM_007019 Hs 93002 98 1379 13805850
449784 ESTs AW161319 Hs 12915 98 4115 7993
406964 FGENES predicted novel secreted protein M21305 98 87884847
439053 chaperonin containing TCP1, subunιt2 ( BE244588 Hs 6456 98 3374 7357
408972 DKFZP586D0919 protein AL050100 Hs 49378 98 2872885008
410687 lysyl oxidase-like 1 U24389 Hs 65436 98 4854865153
448386 KIAA1329 protein AB037750 Hs 21061 98 399739987896
407656 Homo sapiens mRNA, cDNA DKFZp434B2119 ( AW747986 Hs 37443 97 148 4893
424086 lysyl oxidase AI351010 Hs 102267 96 1896 6227
431211 gap junction protein, beta 2, 26kD (con M86849 Hs 323733 96 27622763 6850
412755 ESTs, Weakly similarto P4HA_HUMAN PROL BE144306 Hs 179891 95 637 5274
426991 Homo sapiens cDNA FLJ10674 fis, clone N AK001536 Hs 214410 95 2294 6502
450098 hypothetical protein FLJ21080 W27249 Hs 8109 94 4134 8009
411296 growth suppressor 1 BE207307 Hs 10114 94 524 5183
409012 DKFZP434I216 protein AL117435 Hs 49725 94 2932945013
413211 hypothetical protein MGC4365 AW967107 Hs 109274 94 689 5318
449077 ESTs AW262836 Hs 252844 94 4063 7947
425130 ESTs AA448208 Hs 99163 93 2050 6335
440502 regulator of G-protein signalling 12 AI824113 Hs 78281 93 3470 7449
449717 cerebral cell adhesion molecule AB040935 Hs 23954 93 41104111 7989
422961 B cell CLL/lymphoma 9 Y13620 Hs 122607 93 1763 17646131
421508 absent in melanoma 2 NM 004833 Hs 1 05115 93 1551 15525977
421155 lysyl oxidase H87879 Hs 102267 93 1512 5950
434096 pleiomorphic adenoma gene like 1 AW662958 Hs 75825 93 3029 7062
433612 Homo sapiens Ku70 binding protein (KUB3 AF078164 Hs 61188 92 2991 29927030
450375 a disintegnn and metalloproteinase dom AA009647 Hs 352537 92 4159 8028
443780 activating transcription factor 5 NM_012068 Hs 9754 92 3643 36447606
445417 a disintegnn like and metalloprotease AK001058 Hs 12680 91 3766 7705
447500 ESTs AI381900 Hs 159212 91 3935 7843
451292 KIAA1295 protein AB037716 Hs 26204 91 4221 42228079
417900 CDC20 (cell division cycle 20, S cerev BE250127 Hs 82906 90 1165 5688
413011 biglycan AW068115 Hs 821 89 669 5302
408989 KIAA0746 protein AW361666 Hs 49500 89 290 5010
449722 cyclin B1 BE280074 Hs 23960 89 4112 7990
431750 ESTs AA514986 Hs 283705 88 2816 6891
431089 ESTs, Weakly similar to unknown proteir BE041395 Hs 374629 88 2745 6838
415701 gamma glutamyl hydrolase (conjugase, fo NM_003878 Hs 78619 88 940941 5514
452701 glutamιne-fructose-6 phosphate traπsami NM_005110 Hs 30332 87 43454346 8178
426369 Kreisler (mouse) maf-related leucine zi AF134157 Hs 169487 86 221322146448
431103 pleiotrophm (hepaππ binding growth fa M57399 Hs 44 86 274827496840
422567 glypican 6 AF111178 Hs 118407 86 1702 17036087
408692 dipeptidylpeptidase VI AL040127 Hs 34074 85 248 4978
412140 RAB6 interacting, kmesin like (rabkine AA219691 Hs 73625 85 573 5223
440099 DKFZP564G202 protein AL080058 Hs 6909 85 345334547434
423600 ESTs AI633559 Hs 310359 85 1824 6177
444931 general transcπption factor IIIA AV652066 HS 75113 85 3735 7681
422087 matrix metalloproteinase 2 (gelatmase X58968 Hs 111301 85 1641 6040
421143 immunoglobulin superfamily containing I AB024536 Hs 102171 85 1510 1511 5949
445302 hypothetical protein FLJ10675 AK001537 Hs 12488 84 375737587699
427099 odd Oz/ten m homolog 2 (Drosophila, mou AB032953 Hs 173560 84 230223036509
439223 UL16 binding protein 2 AW238299 Hs 250618 84 3383 7366
452862 ADAMTS2 (a disintegπn-like and metall AW378065 Hs 8687 83 4360 8190
452683 progesterone membrane binding protein AI089575 Hs 374574 83 4341 8175
454140 hypothetical protein FLJ10474 AB040888 Hs 41793 83 449344948301
452017 prostate cancer associated protein 7 AF109302 Hs 27495 83 4270 8117
453018 ESTs, Weakly similar to Trad [H sapiens AA054522 Hs 61581 83 4379 8207
430055 ESTs BE539656 Hs 283705 83 2644 6767
423217 collagen, type VII, alpha 1 (epidermoly NM_000094 Hs 1 640 83 1784 17856147
431866 angiopoietm-like 2 NMJ12098 Hs 8025 82 28302831 6902
418932 cadhenn 4, type 1 , R cadhenn (retinal L34059 Hs 89484 82 1285 12865777
439070 ESTs A1733278 Hs 7621 82 3375 7358
457869 Homo sapiens, alpha-1 (VI) collagen AU077186 Hs 108885 82 4561 8359
424126 ESTs AA335635 Hs 96917 8 1 1902 6231
422627 transforming growth factor, beta induce BE336857 Hs 118787 81 1715 6097
417866 collagen, type XI, alpha 1 AW067903 Hs 82772 8 1 1162 5685
445900 Homo sapiens clone 24787 mRNA sequence AF070526 Hs 125036 8 1 3803 7733
407756 ubiquitm specific protease 18 AA116021 Hs 38260 81 159 4903
459702 gb an03c03 x1 Stratagene schizo brain S AI204995 8 1 4596 8393
443426 chromosome 20 open reading frame 1 AF098158 Hs 9329 8 1 3621 36227586
423739 ESTs AA398155 Hs 97600 81 1842 6190
417059 extracellular matrix protein 1 AL037672 Hs 81071 80 1067 5611
445537 EGF-like domain, multiple 6 AJ245671 Hs 12844 80 37803781 7716
438451 ESTs AI081972 Hs 220261 80 3323 7313
424916 ESTs AW867440 Hs 23096 80 2028 6319
416349 myomesin (M-protem) 2 (165kD) X69089 Hs 79227 79 991 9925556
400242 Eos Control Hs 144700 79 4605
428289 complement component 2 M26301 Hs 2253 79 2421 24226603 447198 ESTs D61523 Hs 283435 79 3898 7814
428182 ESTs, Weakly similar to GGC1-.HUMAN G AN BE386042 Hs 293317 79 2403 6588
409041 Hypothetical protein, XPJ51860 (KIAA11 AB033025 Hs 50081 79 2993005017
417849 nidogen 2 AW291587 Hs 82733 79 1161 5684
444371 forkhead box M1 BE540274 Hs 239 79 3696 7651
437898 ESTs W81260 Hs 43410 78 3293 7286
408349 homeo box C10 BE546947 Hs 44276 78 213 4949
417675 similar to murine leucine-πch repeat p AI808607 Hs 3781 78 1144 5670
449353 ESTs AA001220 Hs 242947 77 4084 7966
427315 Homo sapiens mRNA, cDNA DKFZp564N0763 AA179949 Hs 17556377 2316 6519
435080 hypothetical protein FLJ 14428 AI831760 Hs 155111 77 3103 7122
444784 ectonucleotide pyrophosphatase/phosphod D12485 Hs 11951 77 372437257673
429500 hexabrachion (tenascin C, cytotactin) X78565 Hs 289114 77 257425756718
403171 C2001472* gι|5809678|gb|AAB418482| (U6 77 4710
421778 actin related protein 2/3 complex, subu AA428000 Hs 283072 76 1591 6003
440594 ESTs AW445167 Hs 126036 76 3475 7453
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 76 209921006369
416700 cathepsin D (lysosomal aspartyl proteas AW498958 Hs 343475 76 1023 5579
425234 ESTs, Weakly similar to I38022 hypothet AW152225 Hs 165909 76 2070 6349
417930 Homo sapiens mRNA for KIAA1870 proti -ιπ, H81136 Hs 334604 76 1169 5691
427747 seπne/threonme kinase 12 AW411425 Hs 180655 76 2365 6557
433447 neuronal pentraxm II U29195 Hs 3281 76 29802981 021
409178 kallikrein 5 BE393948 Hs 50915 75 319 5032
452828 ESTs, Weakly similar to KIAA1528 protei W30807 Hs 32374 75 4354 8185
421743 DKFZP564I1171 protein T35958 Hs 107614 75 1586 5998
416561 holocarboxylase synthetase (biotin [pro D87328 Hs 79375 75 1013 10145572
429990 DKFZP547E1010 protein AL050260 Hs 323817 75 263426356760
435767 ESTs H73505 Hs 117874 75 3151 7161
409103 XAGE-1 protein AF251237 Hs 112208 75 3043055021
419682 paired like homeodomam transcription f H13139 Hs 92282 75 1368 5841
410581 tumor endothelial marker 7 precursor AA018982 Hs 125036 75 478 5146
413595 ESTs AW235215 Hs 16145 75 731 5348
407896 Zic family member 1 (odd-paired Drosoph D76435 Hs 41154 74 176 1774919
425588 ESTs F07396 Hs 6627 74 2120 6383
421570 hypothetical protein FLJ21919 AL080172 Hs 105894 74 1566 5986
406673 major histocompatibility complex, class M34996 Hs 198253 74 9091 4821
428189 ESTs AA424030 Hs 46627 74 2404 6589
429609 cell adhesion molecule with homology to AF002246 Hs 210863 74 258425856725
447070 ESTs AI871458 Hs 200022 74 3886 7803
425308 receptor tyrosine kmase-like orphan re M97639 Hs 155585 74 20872088 6362
448961 ESTs AI610643 Hs 187285 74 4052 7937
428834 ESTs AW899713 Hs 10338 74 2479 6647
403907 Autosomal Highly Conserved Protein 73 4732
407824 Homo sapiens cDNA FLJ14388 fis, clone H AA147884 Hs 9812 73 166 4910
422048 spondin 2, extracellular matrix protein NM 012445 Hs 288126 73 1631 1632 6034
427335 G antigen 7B AA448542 Hs 278444 73 2317 6520
414219 ALL1 -fused gene from chromosome 1q W20010 Hs 75823 73 789 5397
412978 homeo box C6 AI431708 Hs 820 73 665 5298
410001 kallikrein 11 AB041036 Hs 57771 73 4034045094
450704 ESTs H85167 Hs 40696 73 4184 8049
452281 Homo sapiens cDNA FLJ11041 fis, clone P T93500 Hs 28792 73 4309 8149
436869 KIAA0711 gene product NMJJ14867 Hs 5333 73 3221 32227222
433435 Ts translation elongation factor, mitoc BE545277 Hs 340959 73 2978 7019
420059 RAB23, member RAS oncogene family AF161486 Hs 94769 73 1412 14135875
404815 ENSP00000251989* DJ100N22 1 (NOVEL EGF- 73 4761
414443 platelet-denved growth factor receptor AU077268 Hs 76144 73 817 5421
442040 UDP-N-acetyl alpha-D-galactosamine poly AW294162 Hs 301062 73 3545 7517
408135 methyltransferase like 1 AA317248 Hs 42957 73 194 4936
432691 mitogen-activated protein kinase 7 U29725 Hs 3080 73 2897 2898 6956
412006 ESTs AW451618 Hs 380683 73 565 5217
433001 clone HQ0310 PRO0310p1 AF217513 Hs 279905 72 292329246977
457411 iroquois class homeobox protein IRX2 AW085961 Hs 130093 72 4549 8349
446921 small inducible cytokine subfamily A (C AB012113 Hs 16530 72 3878 38797797
424408 collagen, type V, alpha 1 AI754813 Hs 146428 72 1943 6260
442573 branched chain ammotransferase 1, cyto H93366 Hs 7567 72 3570 7541
444301 aspoπn (LRR class 1) AK000136 Hs 10760 72 3691 36927647
409142 SMC4 (structural maintenance of chromos AL136877 Hs 50758 72 3123135027
423225 Thy-1 cell surface antigen AA852604 Hs 125359 72 1786 6148
436252 Homo sapiens cDNA FLJ 11562 fis clone H A1539519 Hs 142827 71 3179 7184
457211 ESTs, Weakly similar to S51797 vasodilε I AW972565 Hs 32399 71 4543 8344
449929 ESTs AA004786 Hs 163792 71 4121 7999
410270 tumor endothelial marker 1 precursor AF279142 Hs 195727 71 4424435121
450506 fibroblast activation protein, alpha NM-.004460 Hs 418 71 41704171 8037
413472 solute carrier family 1 (glial high aff BE242870 Hs 75379 71 725 5342
438866 tissue inhibitor of metalloproteinase 2 U44385 Hs 6441 71 33603361 7344
419703 ESTs AI793257 Hs 128151 71 1375 5847
419745 slug (chicken homolog), zinc finger pro AF042001 Hs 93005 7 1 1381 13825851
409637 Homo sapiens mRNA, cDNA DKFZp434K0621 AA323948 Hs 55407 70 372 5069
410611 KIAA1628 protein AW954134 Hs 20924 70 480 5148
429415 procollageπ C-endopeptidase enhancer NM 002593 Hs 202097 70 25572558 6706
452083 ESTs AA022668 Hs 349970 70 4284 8127
411704 hypothetical protein FLJ10074 AI499220 Hs 71573 70 547 5202
408829 heparan sulfate (glucosamine) 3 O sulfo NM-.006042 Hs 48384 70 2642654991
416322 pyrrolιne-5 carboxylate reductase 1 BE019494 Hs 79217 69 989 5554
454033 homeo box HB9 AF107457 Hs 37035 69 4483 8292
445784 ESTs AI253155 Hs 146065 69 3798 7728 436748 collagen, type VI, alpha 2 BE159107 Hs 159263 69 3212 7213
451304 collagen, type XVI, alpha 1 M92642 Hs 26208 69 42244225 8081
422901 nbosomal protein L44 R81936 Hs 75874 69 1757 6126
417389 midkine (πeunte growth-promoting facto BE260964 Hs 82045 69 1109 5647
429294 Homo sapiens cDNA FLJ22463 fis, clone AA095971 Hs 198793 69 2540 6693
421913 osteoglycm (osteoinductive factor, mim AI934365 Hs 109439 68 1611 6020
429973 ESTs AI423317 Hs 164680 68 2628 6756
453642 dipeptidylpeptidase VI AI370936 Hs 34074 68 4431 8251
415885 KIAA0161 gene product D79983 Hs 78894 68 9539545524
449780 nbosomal protein L44 AA443241 Hs 75874 68 4114 7992
426600 VGF nerve growth factor inducible NM 003378 Hs 1 71014 68 22552256 6475
437574 hypothetical protein FLJ21195 similar t AI797592 Hs 207407 68 3272 7266
429441 lipophilm B (uteroglobm family member AJ224172 Hs 204096 68 25602561 6708
418203 CDC28 protein kinase 2 X54942 Hs 83758 68 1202 12035719
416658 fibπlliπ 2 (congenital contractural ar U03272 Hs 79432 68 1020 1021 5577
422562 AE-bindmg protein 1 AI962060 Hs 118397 68 1700 6085
452973 ESTs H88409 Hs 40527 68 4375 8203
414172 phosphatidylinositol glycaπ, class C AW954324 Hs 75790 68 785 5393
428248 ESTs AH 26772 Hs 40479 67 2414 6596
443883 serine (or cysteine) proteinase inhibit AA114212 Hs 9930 67 3653 7614
422007 ESTs AI739435 Hs 39168 67 1624 6029
417944 collagen type V, alpha 2 AU077196 Hs 82985 67 1172 5693
424915 ESTs R42755 Hs 23096 67 2027 6318
453175 RAB32, member RAS oncogene family NM 006834 Hs 32217 67 44004401 8225
421552 secreted frizzled related protein 4 AF026692 Hs 105700 67 1559 1560 5982
452106 ESTs A1141031 Hs 21342 66 4289 8131
422890 ankyπn 3, node of Ranvier (ankyππ G) Z43784 Hs 351357 66 1756 6125
425708 hypothetical protein FLJ22530 AK001342 Hs 14570 66 212821296388
407811 cysteine knot superfamily 1, BMP antago AW190902 Hs 40098 66 164 4908
418478 cycl -dependent kinase inhibitor 2A (m U38945 Hs 1174 66 1245 12465747
420888 dihydropyπmidinase like 4 AB006713 Hs 100058 66 1486 14875930
429451 heme oxygenase (decycl g) 1 BE409861 Hs 202833 66 2562 6709
422106 Fc fragment of IgG binding protein D84239 Hs 111732 65 1646 16476044
450785 Homo sapiens, alpha-1 (VI) collagen AA852713 Hs 108885 65 4193 8056
428317 ESTs AW022609 Hs 50745 65 2431 6610
421823 ESTs N40850 Hs 28625 65 1600 6011
418322 cyclm-dependent kinase inhibitor 3 (CD AA284166 Hs 84113 65 1214 5727
426968 amphiphysin (Stiff-Mann syndrome with b U07616 Hs 173034 65 22902291 6499
442295 Homo sapiens cDNA FLJ11469 fis, clone H AI827248 Hs 224398 65 3555 7527
400419 Target AF084545 65 22234626
407604 collagen, type VIII, alpha 2 AW191962 Hs 353001 65 145 4891
450847 stanniocalcm 1 NM_003155 Hs 25590 65 4201 42028062
416391 mesoderm specific transcript (mouse) ho AI878927 Hs 79284 65 999 5562
422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 65 1734 6110
420576 KIAA1858 protein AA297634 Hs 54925 65 1463 5914
441020 ESTs W79283 Hs 35962 64 3495 7471
408118 calcium binding protein Cab45 precursor T23064 Hs 42806 64 192 4934
409433 ESTs AA074382 Hs 135255 64 349 5053
432239 matrix metalloproteinase 13 (collageπas X81334 Hs 2936 64 2856 28576921
434652 bladder cancer overexpressed protein AF148713 Hs 125830 64 306630677092
438459 Homo sapiens cDNA FLJ13655 fis, clone P T49300 Hs 35304 64 3325 7315
417605 regulator of G protein signalling 3 AF006609 Hs 82294 64 1138 11395665
424420 prostaglaπdm E synthase BE614743 Hs 146688 64 1949 6264
425964 progesterone membrane binding protein AW889928 Hs 9071 64 2157 6408
433078 Homo sapiens cDNA FLJ12231 fis, clone M AW015188 Hs 121575 64 2938 6988
442432 hypothetical protein FLJ23468 BE093589 Hs 38178 63 3563 7535
452046 KIAA0802 protein AB018345 Hs 27657 63 427542768120
402992 Target Exon 63 4700
426363 transforming growth factor, beta 3 M58524 Hs 2025 63 22102211 6446
451253 claudiπ 10 H48299 Hs 26126 63 4220 8078
412104 Homo sapiens, Similar to RIKEN cDNA 221 AW205197 Hs 240951 63 569 5220
418110 hypothetical protein FLJ22202 R43523 Hs 217754 63 1193 5710
451763 hypothetical protein FLJ 14220 AW294647 Hs 233634 63 4254 8103
419750 Homo sapiens cDNA FLJ14236 fis, clone N AL079741 Hs 183114 63 1385 5853
408212 hypothetical protein AA297567 Hs 43728 63 206 4945
427751 conserved gene amplified in osteosarcom AF000152 Hs 355816 63 2366 23676558
431124 doublesex and mab-3 related transcπpti AF284221 Hs 59506 63 2753 27546843
434377 mtron of peπostin (OSF-2os) AW137148 Hs 306593 62 3051 7078
413436 sphmgosine kinase 1 AF238083 Hs 68061 62 721 7225339
439285 hypothetical protein FLJ20093 AL133916 Hs 47860 62 3389 7372
431183 KDEL (Lys Asp Glu-Leu) endoplasmic reti NMJ506855 Hs 250696 62 275627576845
431347 insulin-like growth factor 2 (somatomed AI133461 Hs 251664 62 2774 6859
426855 Homo sapiens mRNA, cDNA DKFZp566P013 AL117427 Hs 172778 62 2279 6491
438085 ESTs R52518 Hs 7967 62 3299 7292
452063 ESTs, Weakly similar to TWSTJHUMAN TWIS R53185 Hs 32366 62 4281 8124
447359 adenylate kinase 5 NM J12093 Hs 1 8268 62 3918 39197830
419156 amelogenin (X chromosome, amelogenesis AC002366 Hs 1238 62 1311 13125797
420005 ESTs AW271106 Hs 133294 62 1407 5871
410867 fibπllin 1 (Marfaπ syndrome) X63556 Hs 750 62 498499 5162
452199 hypothetical protein MGC3133 BE255643 Hs 110695 62 4297 8139
410240 synaptojanin 2 AL157424 Hs 61289 61 437 5117
447733 MAD2 (mitotic arrest deficient, yeast, AF157482 Hs 19400 61 395539567860
424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs 93135 6 1 1907 6235
418283 cathepsm K (pycπodysostosis) S79895 Hs 83942 61 1210 1211 5724
426935 collagen, type I, alpha 1 NM 000088 Hs 1 72928 61 228822896498
450447 hypothetical protein P15-2 AF212223 Hs 25010 61 41684169 8036 417437 interferon regulatory factor 4 U52682 Hs 82132 61 1123 11245656
401797 Target Exon 61 4663
421251 enigma (LIM domain protein) Z28913 Hs 102948 61 1521 5957
427060 ESTs AW378993 Hs 90286 6 1 2300 6507
436311 ESTs AA708958 Hs 168732 61 3181 7186
434629 glioma-amplified sequence 41 AA789081 Hs 4029 6 1 3064 7090
410295 nidogen (enactin) AA741357 Hs 356624 6 1 450 5127
401131 NM-.001651* Homo sapiens aquapoπn 5 (AQ 61 4644
421579 stem cell growth factor, lymphocyte sec NM 002975 Hs 1 05927 60 1567 15685987
429707 matrix metalloproteinase 23B W76631 Hs 211819 60 2606 6738
428046 ESTs, Moderately similar to I38022 hypo AW812795 Hs 337534 60 2393 6579
444734 7-dehydrocholesterol reductase NM 001360 Hs 1 1806 60 371837197669
451766 ephrιπ-B3 NMJ01406 Hs 26988 60 425542568104
449294 ESTs AI651786 Hs 195045 60 4079 7961
410361 guanylate binding protein 1, interferon BE391804 Hs 62661 60 456 5132
451149 RNA binding motif protein 8B AL047586 Hs 10283 60 4214 8073
453164 SNARE associated protein snapm F33692 Hs 32018 60 4396 8222
446211 S100 calcium-binding protein A13 AI021993 Hs 14331 60 3824 7752
407083 H sapiens XG mRNA (clone PEP11) Z48511 60 107 4859
456508 ESTs, Weakly similar to AF208855 1 BM 0 AA502764 Hs 123469 60 4521 8325
452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 60 43104311 8150
452160 cysteine sulfiπic acid decarboxylase re BE378541 Hs 355568 60 4292 8134
449318 Homo sapiens, Similar to RIKEN cDNA 573 AW236021 I Hs 78531 60 4080 7962
442743 ESTs, Weakly similar to MUC2JHUMAN MUCI AI801351 Hs 302110 6 0 3583 7551
419169 ESTs, Weakly similar to S72482 hypolhet AW851980 Hs 262346 59 1314 5799
445363 tubulin specific chaperone d NM 005993 Hs 1 2570 59 376237637702
432731 fibronectin 1 R31178 Hs 287820 59 2904 6961
425760 galactosamme (N-acetyl) 6 sulfate sulf D17629 Hs 159479 59 21342135 6392
402855 NM_001839* Homo sapiens calponm 3, aci 59 4694
438203 ESTs BE540090 Hs 7345 59 3308 7300
428450 KIAA0175 gene product NMJ.14791 Hs 1 84339 59 244324446621
434879 collagen, type VI, alpha 2 M34572 Hs 159263 59 308630877107
422809 hypothetical protein FLJ10549 AK001379 Hs 121028 59 1741 17426115
423905 lung type I cell membrane-associated gl AW579960 Hs 135150 59 1867 6207
415758 protein kinase C, zeta BE270465 Hs 78793 59 946 5518
427871 Homo sapiens, clone IMAGE 3507281 , mRNA AW992405 Hs 35240659 2380 6568
458956 gb ht98f11 x1 NCI CGAP_Lu24 Homo sapien BE220675 59 4587 8383
426798 ESTs AA385062 Hs 130260 58 2275 6487
424440 ESTs AA340743 Hs 133208 58 1951 6266
445875 Homo sapiens clone 24453 mRNA sequence AF070524 Hs 13410 58 3801 7731
420139 lipase, hormone-sensitive NM 005357 Hs 95351 58 1419 14205881
439897 KIAA0942 protein NMJ15310 Hs 6763 58 34373438 7420
432527 ESTs AW975028 Hs 102754 58 2883 6944
428398 ESTs AI249368 Hs 98558 58 2435 6614
432576 ESTs, Weakly similar to I38022 hypothet AW157424 Hs 165954 58 2888 6949
421848 collagen, type VI, alpha 1 X15880 Hs 108885 58 1602 1603 6013
404245 NM_007116* 58 4743
408901 hypothetical protein FLJ 10468 AK001330 Hs 48855 58 2722734997
439979 hypothetical protein FLJ10430 AW600291 Hs 6823 58 3442 7424
452436 ESTs, Moderately similar to A46010 X Ii BE077546 Hs 31447 58 4330 8164
432211 hypothetical protein FLJ10986 BE274530 Hs 273333 58 2852 6917
425398 hypothetical protein similarto tenasci AL049689 Hs 156369 58 2101 2102 6370
447757 KIAA0859 protein AA071276 Hs 19469 58 3960 7863
434775 ESTs AA648983 Hs 370514 58 3074 7098
422586 hypothetical protein FLJ22127 AA312704 Hs 59457 58 1709 6091
441669 Homo sapiens cDNA FLJ11436 fis, clone H R78195 Hs 29692 58 3532 7504
424066 ESTs, Weakly similar to I38022 hypothet Z99348 Hs 112461 58 1891 6223
422201 G protein coupled receptor 30 NM 001505 Hs 1 13207 57 1658 16596054
449378 ESTs AW664026 Hs 59892 57 4085 7967
421815 membrane protein CH1 AW592146 Hs 108636 57 1598 6009
408792 coagulation factor X L29433 Hs 47913 57 260261 4988
409190 sarcoma amplified sequence AU076536 Hs 50984 57 321 5034
435232 cyclin dependent kinase inhibitor 2C (p NM 001262 Hs 4854 57 311431157132
411893 ESTs R82845 Hs 273789 57 558 5211
428959 WNT1 inducible signaling pathway protei AF100779 Hs 194680 57 249324946657
421686 KIAA0584 protein AB011156 Hs 106794 57 1578 1579 5993
418113 SRY (sex determining region Y) box 4 AI2721 1 Hs 83484 57 1194 5711
433842 ESTs AI652156 Hs 26346 57 3009 7044
409664 ESTs AA076743 Hs 129770 57 374 5071
427855 KIAA1877 protein R61253 Hs 98265 57 2376 6565
453880 ESTs, Weakly similar to I38022 hypothet AI803166 Hs 135121 57 4458 8272
410169 hypothetical protein MGC3047 AI373741 Hs 59384 57 428 5112
409731 thymosm, beta, identified in neuroblas AA125985 Hs 56145 57 386 5080
414001 ESTs, Moderately similar to ALU1 HUMAN AI610347 Hs 103812 57 762 5374
409125 axoπal transport of synaptic vesicles R17268 Hs 343567 57 308 5024
421991 KIAA0990 protein NMJ14918 Hs 1 10488 56 162216236028
414359 cadhenn 11, type 2, OB cadhenn (osteo M62194 Hs 75929 56 808 5413
412446 ESTs AI768015 Hs 352375 56 586 5235
419511 general transcπption factor IIIA AA429750 Hs 75113 56 1345 5824
428981 ESTs, Weakly similar to ALU2_HUMAN ALU BE313077 Hs 93135 56 2497 6660
407862 Homo sapiens cDNA FLJ10934 fis, clone O BE548267 Hs 337986 56 171 4915
410711 KIAA0318 protein AB002316 Hs 65746 56 489490 5155
446102 ESTs AW168067 Hs 317694 56 3819 7747
411756 discoidm domain receptor family, membe BE294350 Hs 71891 56 550 5205
410929 ESTs H47233 Hs 30643 56 504 5166
431789 mitogen-activated protein kinase 4 H19500 Hs 269222 56 2821 6895 418986 ESTs AI123555 Hs 293821 56 1288 5779
401130 Target Exon 56 4643
425131 ESTs BE252230 Hs 99163 56 2051 6336
433430 ESTs AI863735 Hs 369982 56 2977 7018
408296 DKFZP586G1517 protein AL117452 Hs 44155 56 2092104947
429299 hypothetical protein MGC13102 AI620463 Hs 347408 56 2541 6694
435460 ESTs AA682439 Hs 118380 56 3126 7142
411789 Adlican AF245505 Hs 72157 56 5535545207
417933 thymidylate synthetase X02308 Hs 82962 56 1170 1171 5692
411335 KIAA1096 protein AA132813 Hs 69559 56 526 5185
431070 transcription factor 19 (SC1) AW408164 Hs 249184 55 2744 6837
434837 lysophosphatidic acid acyltransferase-d AF156776 Hs 353175 55 30803081 7102
400245 Eos Control Hs 7957 55 4607
423633 ESTs N39053 Hs 164146 55 1830 6182
418097 ESTs R45137 Hs 279789 55 1191 5708
410096 hypothetical protein MGC5540 AW245200 Hs 267400 55 420 5105
429965 Homo sapiens cDNA FLJ11789 fis, clone H AL040379 Hs 99551 55 2627 6755
452839 nbosomal protein L44 R96290 Hs 75874 55 4359 8189
426386 bladder cancer overexpressed protein AA748850 Hs 125830 55 2216 6450
439999 ras homolog gene family, member E AA115811 Hs 6838 55 3444 7426
426013 ESTs AI818098 Hs 4779 55 2160 6410
426509 pentaxin-related gene, rapidly induced M31166 Hs 2050 55 224322446468
407874 Homo sapiens cDNA FLJ14059 fis, clone H AI766311 Hs 289047 55 175 4918
427378 melanoma antigen, family D, 1 BE515037 Hs 177556 55 2322 6523
414053 transgelin 2 BE391635 Hs 75725 55 774 5383
411894 GLl-Kruppel family member GLI3 (Greig c M57609 Hs 72916 55 5595605212
432692 ESTs AW974944 Hs 285814 55 2899 6957
426155 ESTs AA370953 Hs 163553 55 2182 6426
411358 KIAA1691 protein R47479 Hs 94761 55 527 5186
449129 ESTs AI631602 Hs 258949 55 4066 7950
432503 ESTs AA551196 Hs 188952 55 2878 6940
439130 ESTs AA306090 Hs 345588 55 3378 7361
448848 hypothetical protein AF131851 Hs 22241 55 404240437931
413053 ESTs, Moderately similar to KIAA1399 pi ; AW963263 Hs 65377 55 674 5306
432693 ESTs AW449630 Hs 293790 55 2900 6958
425428 DKFZP586B0621 protein AL110261 Hs 157211 55 210421056372
451952 ESTs AL120173 Hs 301663 55 4264 8111
408562 roundabout (axon guidance receptor, Dro AI436323 Hs 31141 55 240 4971
441607 neuronal cell adhesion molecule NM 05010 Hs 7912 55 352635277499
427596 extracellular glycoprotein EMILIN-2 pre AA449506 Hs 270143 55 2350 6544
422532 protective protein for beta galactosida AL008726 Hs 118126 55 1697 16986083
457500 protein kinase, interferon inducible do NM 02759 Hs 274382 55 455545568354
435538 low density lipoprotein receptor-relate AB011540 Hs 4930 55 313231337148
448520 doublecortin and CaM kinase like 1 AB002367 Hs 21355 55 40104011 7907
415689 ESTs AW959615 Hs 111045 55 938 5512
409248 KIAA1209 protein AB033035 Hs 51965 55 330331 5040
408660 ESTs Moderately similar to PC4259 ferr AA525775 Hs 89040 55 247 4977
445162 piccolo (presynaptic cytomatrix protein AB011131 Hs 12376 55 374937507693
449029 solute carrier family 7 (cationic ammo N28989 Hs 22891 55 4058 7942
400288 integrin, alpha 5 (fibronectin receptor X06256 Hs 149609 54 1 4614
400295 AI905687 IL-BT095-190199 019 BT095 Homo W7283Ϊ i Hs 348419 54 6 4617
445439 regulator of nonsense transcripts 1 BE243084 Hs 12719 54 3770 7708
419726 bone morphogenetic protein 1 U50330 Hs 1274 54 1376 13775848
431457 mtegπn, alpha 11 NM.012211 Hs 256297 54 278727886870
417412 interleukin 1 receptor, type I X16896 Hs 82112 54 1116 11175652
417259 chondroitin sulfate proteoglycan 2 (ver AW903838 Hs 81800 54 1092 5632
418867 msh (Drosophila) homeo box homolog 2 D31771 Hs 89404 54 1277 12785772
447709 GDNF family receptor alpha 2 U97145 Hs 19317 54 394939507856
430439 DKFZP434B061 protein AL133561 Hs 380155 54 269526966803
429207 ESTs AA447941 Hs 123423 54 2532 6686
444006 type I transmembrane protein Fn14 BE395085 Hs 334762 54 3668 7627
410889 twist (Drosophila) homolog (acrocephalo X91662 Hs 66744 54 501 5025164
427585 collagen, type X, alpha 1 (Schmid metap D31152 Hs 179729 54 2349 6543
429101 uterine derived 14 kDa protein AW452174 Hs 173780 54 2513 6672
447197 gb yh88b01 s1 Soares placenta Nb2HP Hom R36075 Hs 358552 54 3897 7813
422648 Melanoma associated gene D86983 Hs 118893 54 1720 1721 6100
426485 platelet-derived growth factor receptor NM_006207 Hs 1 70040 54 223822396465
421787 nuclear receptor subfamily 2, group C, AA227068 Hs 108301 54 1594 6006
408741 carboxypeptidase A3 (mast cell) M73720 Hs 646 54 2522534982
443184 ESTs A1638728 Hs 135159 54 3607 7574
433895 mitogen-activated protein kinase kinase AI287912 Hs 3628 54 3014 7048
453596 hypothetical protein FLJ14834 AA441838 Hs 62905 54 4428 8248
424001 paternally expressed 10 W67883 Hs 137476 54 1882 6217
411263 kinesm-like 6 (mitotic centromere-asso BE297802 Hs 69360 53 523 5182
447414 neuroblastoma (nerve tissue) protein D82343 Hs 74376 53 392439257834
450296 hepatocyte growth factor-regulated tyro AL041949 Hs 24756 53 4153 8023
421506 thymidine kinase 1, soluble BE302796 Hs 105097 53 1550 5976
424192 P311 protein U30521 Hs 142827 53 1911 19126238
416140 roundabout (axon guidance receptor, Dro AI918035 Hs 301198 53 978 5545
452877 ESTs AI250789 Hs 32478 53 4364 8193
433819 ESTs AW511097 Hs 110069 53 3007 7042
440856 ESTs AW993377 Hs 130390 53 3489 7465
432101 EphA3 A1918950 Hs 123642 53 2841 6909
432988 ESTs, Weakly similar to IDN4-GGTR14 [H R39234 Hs 251699 53 2921 6975
426514 bone morphogenetic protein 7 (osteogeni BE616633 Hs 170195 53 2246 6470
431117 delta (Drosophila) like 1 AF0O3522 Hs 250500 53 2751 27526842 434269 similar to muπne leucine-nch repeat p AK001991 Hs 3781 53 303730387069
420255 membrane metallo-endopeptidase (neutral NM 007289 Hs 1298 53 1438 14395896
438828 hypothetical protein DKFZp761 F2014 AL134275 Hs 6434 53 3356 7340
400297 hypothetical protein DKFZp56401278 AI127076 Hs 288381 53 7 4618
422100 ADP-πbosylatioπ factor-like 7 AI096988 Hs 111554 53 1644 6042
441944 Homo sapiens clone 23767 and 23782 mRNA AW855861 Hs 8025 53 3541 7513
407603 Homo sapiens, clone IMAGE 4299322, mRNA AW955705 Hs 62604 53 144 4890
453830 ESTs AA534296 Hs 20953 53 4445 8263
456181 ras inhibitor L36463 Hs 1030 53 451645178321
412773 similar to vaccinia virus Hmdlll K4L O H15785 Hs 74573 53 639 5276
419405 ESTs AI377043 Hs 42189 53 1333 5816
432791 sentπn/SUMO specific protease NMJ14554 Hs 66450 53 290729086963
419999 ESTs AI760942 Hs 191754 53 1406 5870
420238 ESTs, Weakly similar to 2109260A B cell AA256783 Hs 12549 53 1436 5894
456063 retmol binding protein 4, interstitial NM 006744 Hs 76461 53 4511 45128317
437342 hypothetical protein DKFZp761K1423 AW903297 Hs 236438 53 3254 7251
423057 ESTs, Moderately similar to I38022 hypo AW961597 Hs 130816 53 1773 6139
426148 Homo sapiens cDNA FLJ10728 fis, clone N A1751071 Hs 167135 53 2179 6424
417153 collagen, type II, alpha 1 (primary ost X57010 Hs 81343 53 1084 10855625
419987 osteomodulm NM 005014 Hs 94070 53 1402 14035868
409170 ESTs W91994 Hs 16145 53 317 5030
414312 ESTs AA155694 Hs 191060 53 800 5407
418452 C-type (calcium dependent carbohydrate BE379749 Hs 85201 53 1241 5744
426471 transforming growth factor, alpha M22440 Hs 170009 52 223322346462
428342 Homo sapiens cDNA FLJ13458 fis, clone P AI739168 Hs 349283 52 2432 6611
444829 ubiquitm specific protease 22 AB028986 Hs 12064 52 372637277674
443191 a disintegnn like and metalloprotease N93301 Hs 155824 52 3608 7575
448197 KIAA1303 protein AB037724 Hs 20677 52 398439857885
414919 ESTs AW087337 Hs 194461 52 890 5474
439319 ESTs AW016401 Hs 2549 52 3392 7375
424898 ESTs H17954 Hs 6664 52 2021 6314
412577 CD163 antigen Z22968 Hs 74076 52 6086095252
419437 neogenm (chicken) homolog 1 U61262 Hs 90408 52 1338 13395820
408161 hypothetical protein MGC3032 AW952912 Hs 300383 52 195 4937
421485 hypothetical protein FLJ10134 AA243499 Hs 104800 52 1547 5974
422550 microfibrillar associated protein 4 BE297626 Hs 296049 52 1699 6084
426716 sema domain, Immunoglobulin domain (lg) NM_006379 Hs 171921 52 22642265 6481
417079 interleukin 1 receptor antagonist U65590 Hs 81134 52 1073 10745616
439668 frizzled (Drosophila) homolog 8 AI091277 Hs 302634 52 3414 7397
452682 progesterone membrane binding protein AA456193 Hs 374574 52 4340 8174
422170 anti-Mulleπan hormone AI791949 Hs 112432 52 1655 6051
407216 lysyl oxidase N91773 Hs 348385 52 123 4875
421233 tetraspaπ NET-6 protein AA209534 Hs 284243 52 1518 5955
436608 down syndrome critical region protein D AA628980 Hs 192371 52 3205 7207
428698 KIAA1866 protein AA852773 Hs 334838 52 2463 6635
414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 52 8768775465
426304 Homo sapiens cDNA FLJ 11477 fis, clone H AA374532 Hs 124673 5 1 2198 6438
449679 tolloid-like 1 AI823951 Hs 129700 51 4106 7986
410108 OSBP-related protein 6 AA081659 Hs 318775 5 1 423 5108
409509 ESTs AL036923 Hs 322710 51 353 5056
434868 collagen, type VI, alpha 2 R50032 Hs 159263 5 1 3085 7106
449897 transmembrane protein vezatm, hypothet AW819642 Hs 24135 5 1 4120 7998
414024 gb zm79g08 r1 Stratagene neuroepithe u AA134712 Hs 22410 51 769 5379
418506 Unknown protein for MGC 29643 (formerly AA084248 Hs 372651 51 1247 5748
433513 ESTs AI566356 Hs 171437 5 1 2985 7024
416406 lipoma HMGIC fusion partner-like 2 D86961 Hs 79299 5 1 1001 10025564
452078 ESTs AA022620 Hs 52170 51 4283 8126
416986 ESTs AI471952 Hs 148676 5 1 1057 5603
429480 elastm (supravalvular aortic stenosis, M36860 Hs 9295 5 1 2565 25666712
439703 ESTs AF086538 Hs 196245 51 3420 7403
414117 proteolipid protein 1 (Pelizaeus-Merzba W88559 Hs 355807 5 1 777 5386
408996 glycoprotein (transmembrane) nmb AI979168 Hs 82226 5 1 291 5011
434431 ESTs AW131454 Hs 168571 51 3056 7082
440676 LIM and senescent cell antigen like dom NM 004987 Hs 1 12378 51 347934807457
447217 neuropilm 2 BE465754 Hs 17778 51 3904 7819
421362 hypothetical protein FLJ20043 AK000050 Hs 103853 51 1531 15325965
441389 endocytic receptor (macrophage mannose AF134838 Hs 7835 51 351435157488
423857 Homo sapiens mRNA, cDNA DKFZp564O0862 N48902 Hs 133481 5 1 1857 6200
410132 Mιcrofibrιl-assocιated glycoproteιπ-2 NMJJ03480 Hs 300946 51 425426 5110
452410 Homo sapiens mRNA, cDNA DKFZp434E2321 (AL133619 Hs 29383 5 1 43284329 8163
423989 OLF-1/EBF associated zinc finger gene AF221712 Hs 137168 51 1880 1881 6216
441362 RAD51 (S cerevisiae) homolog (E coli R ; BE614410 Hs 23044 5 1 3512 7486
426283 kynurenmase (L-kynurenine hydrolase) NM 003937 Hs 1 69139 50 219221936435
435854 putative aπkyrm-repeat containing prot AJ278120 Hs 4996 50 315731587166
448425 ESTs AI500359 Hs 371249 50 4004 7901
439332 Homo sapiens mRNA, cDNA DKFZp547M072 (f AW842747 Hs 378821 50 3393 7376
422565 singed (Drosophila) like (sea urchin fa BE259035 Hs 118400 50 1701 6086
450746 general transcription factor II i D82673 Hs 278589 50 4187 8051
421822 coagulation factor XI (plasma thrombopl AV650066 Hs 1430 50 1599 6010
452958 ESTs AA883929 Hs 40527 50 4372 8200
448410 hypothetical protein FLJ20220 AK000227 HS 21126 50 40004001 7898
437829 ESTs AI358522 Hs 103834 50 3289 7282
426479 mouse double minute 2, human homolog of Z12020 Hs 170027 50 223522366463
446512 ESTs H30351 Hs 207982 50 3848 7771
437139 ESTs, Weakly similar to RTA RAT PROBABL W73685 Hs 118513 50 3238 7236
442657 ESTs BE502631 Hs 130645 50 3576 7546 436291 protein regulator of cytokinesis 1 BE568452 Hs 344037 50 3180 7185
408988 Homo sapiens clone TUA8 Cn du chat reg AL119844 Hs 49476 50 289 5009
408968 hypothetical protein FLJ20644 AI652236 Hs 49376 50 286 5007
441368 ESTs AA931532 Hs 126836 50 3513 7487
420737 CD70 , tumor necrosis factor (ligand) L08096 Hs 99899 50 1473 14745920
420173 ESTs AA256151 Hs 22999 50 1426 5886
443920 Homo sapiens cDNA FLJ13655 fis, clone P AL037764 Hs 35304 50 3659 7620
435370 ESTs AI964074 Hs 225838 50 3120 7136
453935 ESTs AI633770 Hs 42572 50 4470 8281
412942 mitogen-activated protein kinase activa AL120344 Hs 75074 50 658 5293
456534 phospholipase C, beta 3, neighbor pseud X91195 Hs 100623 50 4522 8326
413094 TOLLIP protein H24184 Hs 25413 50 680 5311
415014 ESTs AW954064 Hs 24951 50 900 5481
412992 protease, serine, 11 (IGF binding) AI423369 Hs 75111 50 666 5299
424512 integrin, beta 5 X53002 Hs 149846 50 196819696277
449969 Homo sapiens cDNA FLJ14337fis, clone P AW295142 Hs 180187 50 4123 8001
448498 ESTs AA418276 Hs 375003 50 4007 7904
418423 KIAA0513 gene product NM_014732 Hs 301658 50 1239 12405743
416051 mannosidase, alpha, class 1A, member 1 AA835868 Hs 25253 50 966 5534
431448 hypothetical protein DKFZp56401278 AL137517 Hs 306201 50 278527866869
423400 Homo sapiens mRNA, cDNA DKFZp434M038 (f AL122123 Hs 12795850 1802 6159
408374 forkhead bo FI AW025430 Hs 155591 50 216 4951
425525 ESTs AA358883 Hs 23871 50 2111 6377
425703 collagen, type VI, alpha 2 X06195 Hs 159263 50 212621276387
457464 ESTs AW972234 Hs 126680 49 4554 8353
419452 PTK7 protein tyrosine kinase 7 U33635 Hs 90572 49 1340 1341 5821
412708 ESTs, Weakly similar to CGHU7L collagen R26830 Hs 106137 49 630 5268
425818 matrix metalloproteinase 17 (membrane i AB021225 Hs 159581 49 214521466398
424876 Homo sapiens clone IMAGE 297403, mRNA s AI056991 Hs 269873 49 2016 6310
426075 ESTs, Weakly similarto 2109260A B cell AW513691 Hs 270149 49 2170 6417
413401 ESTs AI361861 Hs 118659 49 712 5332
421680 Human DNA sequence from clone CTA-984G1 AL031186 Hs 289106 49 1576 15775992
402233 NM_030760* Homo sapiens endothelial dif 49 4674
414945 lymphocyte antigen 6 complex locus E BE076358 Hs 77667 49 894 5477
427254 ESTs AL121523 Hs 97774 49 2312 6516
432290 Homo sapiens cDNA FLJ10237 fis, clone H AK001099 Hs 274273 49 2862 6926
448888 caspase recruitment domain protein 6 AW196663 Hs 200242 49 4049 7935
451333 hypothetical protein FLJ10052 AK000914 Hs 26244 49 422642278082
447436 Homo sapiens cDNA FLJ21449 fis, clone AI932971 Hs 18593 49 3928 7837
402507 Target Exon 49 4683
427557 plasminogen activator, urokinase recept NM 002659 Hs 1 79657 49 234323446539
428411 ESTs AW291464 Hs 10338 49 2439 6617
418216 AF15q14 protein AA662240 Hs 283099 49 1206 5721
440952 ESTs AI291804 Hs 118101 49 3490 7466
422684 H2A histone family, member Z BE561617 Hs 119192 49 1726 6105
442173 KIAA0144 gene product N76101 Hs 8127 49 3552 7524
451743 ESTs AW074266 Hs 336428 49 4251 8101
438545 KIAA1151 protein AB032977 Hs 6298 49 332933307319
424242 hypothetical protein MGC13102 AA337476 Hs 347408 49 1921 6243
453392 SRY (sex determining region Y) box 11 U23752 Hs 32964 49 441644178239
447270 general transcription factor HIC poly AC002551 Hs 331 49 39103911 7824
424765 hypothetical protein FLJ14033 similar t AA428211 Hs 371383 49 1998 6297
403909 Autosomal Highly Conserved Protein 49 4734
423464 CSR1 protein NMJ16240 Hs 1 28856 48 1809 1810 6165
439456 hypothetical protein FLJ20980 AI752409 Hs 109314 48 3400 7383
429612 pituitary tumor-transforming 1 AF062649 Hs 252587 48 258625876726
452526 hypothetical protein MGC3040 W38537 Hs 280740 48 4336 8170
411975 ESTs AI916058 Hs 144583 48 564 5216
412359 gb QV3-LT0048-l40200-083-e05 LT0048 HomAW837985 Hs 56729 48 583 5232
450812 MCF 2 cell line derived transforming se AB002360 Hs 25515 48 419641978058
417534 myosin IE NM_004998 Hs 8 2251 48 1131 11325660
426400 Homo sapiens clone 25121 neuronal olfac M78361 Hs 169743 48 2218 6452
453874 collagen, type XIV, alpha 1 (undulin) AW591783 Hs 36131 48 4456 8270
434924 hypothetical protein FLJ13433 AA443164 Hs 23259 48 3093 7112
421483 hypothetical protein MGC11333 NM.003388 Hs 1 04717 48 154515465973
418007 matrix metalloproteinase 1 (iπterstitia M13509 Hs 83169 48 1177 11785697
420261 fibroblast growth factor receptor 1 (fm AW206093 Hs 748 48 1440 5897
451957 Homo sapiens cDNA FLJ13545 fis, clone P AI796320 Hs 10299 48 4265 8112
452055 hypothetical protein MGC10858 AI377431 Hs 141693 48 4279 8122
444783 anillin (Drosophila Scraps homolog), ac AK001468 Hs 62180 48 372237237672
456346 ESTs AW974998 Hs 222430 48 4519 8323
448140 BCM-like membrane protein precursor AF146761 Hs 20450 48 39803981 7882
427474 aggrecan 1 (chondroitin sulfate proteog U13192 Hs 2159 48 2334 6532
418672 ESTs L44284 Hs 12915 48 1266 5763
426064 Homer, neuronal immediate early gene, 3 BE387014 Hs 166146 48 2168 6415
418327 paired-like homeodomam transcription f U70370 Hs 84136 48 1217 12185729
429351 hypothetical protein FLJ10628 AK001490 Hs 200016 48 25492550 6701
431429 reticulon 3 AF072813 Hs 252831 48 2783 6867
437623 chromosome condensation related SMC-ass D63880 Hs 5719 48 32753276 7269
409361 sine oculis homeobox (Drosophila) homol NM 005982 Hs 54416 48 3443455049
442572 hypothetical protein FLJ22415 AI001922 Hs 135121 48 3569 7540
433797 ESTs AA609579 Hs 112724 48 3003 7039
451052 Homo sapiens cDNA FLJ22165 fis, clone AA281504 Hs 24444 48 4208 8068
421535 phosphoribosylformylglycinamidine synth AB002359 Hs 105478 48 1557 15585981
442619 ESTs, Weakly similar to AF164793 1 prot AA447492 Hs 20183 48 3575 7545
428648 potassium voltage gated channel, subfam AF052728 Hs 188021 47 245924606632 400615 TargetExon 47 4634 446497 ESTs AV658647 Hs 34226 47 38417766 410422 Homosapiens,clone MGC 15203, mRNA, co AL042014 Hs 63348 47 4625136 432842 hypothetical protein MGC4485 AW674093 Hs 334822 47 29116966 435021 ESTs AA922192 Hs 3962 47 30977116 450755 ESTs AA010984 Hs 159464 47 41908054 441266 Homosapiens, cloneIMAGE 3502329, mRNAH15968 Hs 293845 47 35057480 425573 serine (or cysteine) proteinase inhibit AB006423 Hs 158308 47 211621176381 415179 gb HUM091 D02B Human fetal brain (TFujiw D80630 47 9165493 422033 claudin 5 (transmembrane protein delete AW245805 Hs 10903 47 16266031 447343 ESTs, Highly similar to S02392 alpha-2- AA256641 Hs 236894 47 39167828 433209 KIAA1474 protein AB040907 Hs 278436 47 295329546999 415115 hypothetical protein AA214228 Hs 127751 47 9105489 414577 hypothetical protein FLJ20992 similar t A1056548 Hs 378938 47 8325433 418156 nuclear receptor subfamily 1 , group I, W17056 Hs 83623 47 11985716 435149 KIAA1150 protein AW401809 Hs 4779 47 31107128 416680 brain abundant, membrane attached signa AW245540 Hs 79516 47 10225578 434577 Homo sapiens cDNA FLJ22487 fis, clone R37316 Hs 179769 47 30627088 459674 gb zp53f03 r1 Stratagene NT2 neuronal p AA180511 47 45958392 405267 NM_007116* 47 4775 413031 phosphofructokmase, muscle BE515051 Hs 75160 47 6715304 450065 transcnptional co activator with PDZ b AL050107 Hs 24341 47 413041318006 441440 ESTs AI807981 Hs 30495 47 35197492 433935 13kDa differentiation-associated protei AF112208 Hs 44163 47 301830197052 447101 ESTs N72185 Hs 44189 47 38907807 438089 nuclear receptor subfamily 1, group I, W05391 Hs 351546 47 3301 7294 440086 v-ral simian leukemia viral oncogene ho NM 005402 Hs 6906 47 345034517432 434558 ESTs AW264102 Hs 39168 47 30617087 451032 Homo sapiens mRNA, cDNA DKFZp564P116 W03692 Hs 323079 47 42068066 439579 gb Homo sapiens full length insert cDNA AF086400 47 34087391 434423 LIM domain only 4 NMJ06769 Hs 3 844 47 305430557081 409829 lymphocyte-specific protein 1 M33552 Hs 56729 47 3893905083 439734 cAMP response element binding protein C AC005013 Hs 149 47 34267409 429305 myelin protein zero-like 1 AF095727 Hs 287832 47 254225436695 408049 desmoplakin (DPI, DPII) AW076098 Hs 345588 47 1874929 435099 flap structure specific endonuclease 1 AC004770 Hs 4756 46 310431057123 422110 secreted protein, acidic, cysteine rich AI376736 Hs 121555 46 16486045 433556 calcium/calmoduliπ dependent protein ki W56321 Hs 111460 46 29877026 435937 ESTs AA830893 Hs 119769 46 31647172 445936 hypothetical protein FLJ22329 BE543594 Hs 367653 46 38067736 414706 IAA0097 gene product AW340125 Hs 76989 46 8545449 441834 KIAA0736 gene product AL138034 Hs 7979 46 35397511 445745 KIAA0455 gene product AB007924 Hs 13245 46 379637977727 433028 AD-017 protein AI199144 Hs 283737 46 29286980 428283 Homo sapiens mRNA cDNA DKFZp564P116 (fAI439096 Hs 32307946 24206602 446142 ESTs A1754693 Hs 145968 46 38207748 447598 ESTs AI799968 Hs 199630 46 39417848 402812 NM_004930* Homo sapiens capping protein 46 4693 406672 major histocompatibility complex, class M26041 Hs 198253 46 43444820 441859 interleukin 4 induced gene-1 protein (F AW194364 Hs 380444 46 35407512 437188 KIAA1814 protein AL080221 Hs 375566 46 32407238 416389 integrin, beta 5 AA180072 Hs 149846 46 9985561 424503 integnn, alpha 5 (fibronectin receptor NM_002205 Hs 1 49609 46 196519666275 452242 gycosyltransferase R50956 Hs 159993 46 43058145 453280 Homo sapiens mRNA, cDNA DKFZp761C082 (fAL157476 Hs 32913 46 44108233 421631 Homo sapiens mRNA, cDNA DKFZp434D0720 ( AL137551 Hs 10625446 15715989 453884 KIAA0186 gene product AA355925 Hs 36232 46 44608274 451050 ESTs AW937420 Hs 351869 46 45888067 428645 ESTs, Weakly similarto 2017205Adιhydr AA431400 Hs 98729 46 24586631 419983 Homo sapiens mR A, cDNA DKFZp586E1624 W55956 Hs 94030 46 14015867 408503 ESTs Weakly similar to T12552 hypothet AW119059 Hs 348603 46 2334964 410600 ESTs, Moderately similar to S65657 alph AW575742 Hs 351676 46 4795147 433882 procoilagen-proline, 2 oxoglutarate 4-d U90441 Hs 3622 46 301230137047 416914 brain and reproductive organ expressed AA344481 Hs 80426 46 10455595 438411 gb ys81o10 r1 Soares retina N2b4HR Homo H91928 Hs 169370 46 33217311 425082 inositol 1 4,5-tπphosphate receptor, t N44238 Hs 102991 46 20486333 445930 Homo sapiens clone 24747 mRNA sequence AF055009 Hs 13456 46 38047734 402794 Target Exon 46 4691 408393 ESTs AW015318 Hs 143509 46 2194953 425274 minichromosome maintenance deficient (m BE281191 Hs 155462 46 20796356 427933 ESTs AW974643 Hs 190571 46 23866573 437664 ESTs, Moderately similar to ALU1_HUMAN AW977714 Hs 380667 46 32777270 402888 Target Exon 46 4698 439195 gb yw28d08 s1 Morton Fetal Cochlea Homo H89360 46 33817364 408920 fibronectin leucine rich transmembrane AL120071 Hs 48998 46 2764999 439593 ESTs BE073597 Hs 124863 46 34107393 446659 ESTs AI335361 Hs 226376 46 38657786 428513 plexin C1 BE220806 Hs 184697 46 24516625 429047 ciliary neurotrophic factor receptor NM W1842 Hs 1 94774 46 250725086668 421292 ESTs, Weakly similar toALU HUMAN ALU AI620485 Hs 136753 45 15235959 453828 ESTs AW970960 Hs 293821 45 44448262 407112 ESTs, Weakly similar to ALU7.HUMAN ALU AA070801 Hs 51615 45 1114863 439737 Homo sapiens mRNA full length insert cD AI751438 Hs 41271 45 3427 7410 403857 Target Exon 45 4730 448595 KIAA0644 gene product AB014544 Hs 21572 45 401540167910 451678 DKFZP564D0764 protein AA374181 Hs 26799 45 4244 8096 430410 tryptase beta 1 AF099144 Hs 347933 45 268926906799 400289 matrix metalloproteinase 10 (stromelysi X07820 Hs 2258 45 344615 417640 protein C receptor, endothelial (EPCR) D30857 Hs 82353 45 1143 5669 429903 cyclin dependent kinase 5, regulatory s AL134197 Hs 93597 45 2616 6746 452110 Homo sapiens cDNA FLJ11309 fis, clone P T47667 Hs 28005 45 4290 8132 445133 ESTs AW157646 Hs 198689 45 3745 7690 448202 Rho guanine nucleotide exchange factor AB002292 Hs 20695 45 398639877886 436808 ESTs AA731602 Hs 120266 45 3217 7218 406646 major histocompatibility complex, class M33600 Hs 375570 45 36374816 440087 hypothetical protein FLJ22678 W28969 Hs 7718 45 3452 7433 442577 ESTs AA292998 Hs 163900 45 3571 7542 436962 DKFZP564I052 protein AW377314 Hs 5364 45 3229 7228 424265 hairy/enhancer-of-split related with YR AF173901 Hs 144287 45 1927 19286247 451399 ESTs AL042110 Hs 10432 45 4228 8083 430209 collagen, type V, alpha 3 AF177941 Hs 235368 45 265926606778 418526 solute earner family 16 (moπocarboxyli BE019020 Hs 85838 45 1251 5752 425074 Homo sapiens cDNA FLJ22165 fis, clone AA495930 Hs 351869 45 2045 6331 435575 tπggeππg receptor expressed on myeloi AF213457 Hs 44234 45 313931407152 402408 NM_030920* Homo sapiens hypothetical pr 45 4681 424308 minichromosome maintenance deficient (S AW975531 Hs 154443 45 19326250 428926 brain-specific angiogenesis inhibitor 1 NM_001702 Hs 1 94654 45 248724886653 410059 a disintegrin-like and metalloprotease NM 007038 Hs 58324 45 4164175103 425272 ESTs, Weakly similarto C35826 hypothet AA354138 Hs 47209 45 20786355 448786 Homo sapiens cDNA FLJ11881 fis, clone H BE048842 Hs 179075 45 40407929 424909 cell division cycle 25B S78187 Hs 153752 45 202420256316 448438 Homo sapiens cDNA FLJ11640 fis, clone H BE613081 Hs 24654 45 40057902 433180 K562 cell deπved leucine-zipper-like p AB038651 Hs 31854 45 294929506997 437470 hypothetical protein DKFZp547D065 AL390147 Hs 134742 45 326732687262 443164 ESTs, Weakly similar to ALU1_HUMAN ALU AI038503 Hs 55780 45 36067573 450254 neuropeptide G protein coupled receptor NMJJ04885 Hs 99231 45 414741488018 417160 proteolipid protein 1 (Pelizaeus-Merzba N76497 Hs 355807 45 10865626 428977 cyclin B2 AK001404 Hs 194698 45 24966659 436895 carbonic anhydrase XII AF037335 Hs 5338 45 322432257224 429163 gb am20a10 s1 Soares_NFL_T_GBC_S1 Homo AA884766 45 25216678 440516 cadhenn 2, type 1 , N cadhenn (neurona S42303 Hs 161 45 347234737451 422737 collagen, type III, alpha 1 (Ehlers-Dan M26939 Hs 119571 45 173017316108 446388 NPD007 protein AA292979 Hs 7788 45 38377763 412896 major histocompatibility complex, class AW804157 Hs 375570 45 6535288 451938 down regulator of transcπption 1 , TBP- AI354355 Hs 16697 45 42638110 411962 gb zk85d12 r1 Soares_pregnanLuterus NbAA099050 45 5635215 426618 smg GDS-ASSOCIATED PROTEIN AL036456 Hs 171374 45 22596477 421389 Homo sapiens cDNA FLJ12777 fis, clone N AA531291 Hs 101064 45 15375968 407721 dual-specificity tyrosine (Y) phosphory Y12735 Hs 38018 45 1531544898 424330 Homo sapiens cDNA FLJ13596 fis, clone P AW073953 Hs 34054 45 19366253 438855 Homo sapiens mRNA, cDNA DKFZp586J021 (f AW946276 Hs 6441 45 33597343 437446 ESTs, Moderately similarto CA1C RAT CO AA788946 Hs 101302 45 32647259 445424 cortactm SH3 domain-binding protein AB028945 Hs 12696 45 376737687706 433859 ESTs AW896758 Hs 273789 45 30107045 417512 glycoprotein (transmembrane) nmb X76534 Hs 82226 45 112711285658 436159 ESTs AI056637 Hs 369849 45 31727178 404913 NM_024408* Homo sapiens Notch (Drosophi 45 4763 428269 ESTs, Moderately similarto ZN91J-IUMAN W35195 Hs 95659 45 24166598 431674 G protein coupled receptor AA098901 Hs 301642 45 28096885 446219 ESTs A1287344 Hs 369078 44 38267754 434175 ESTs AW979081 Hs 165469 44 30327065 419733 Homo sapiens cDNA FLJ14415 fis, clone H AW362955 Hs 356547 44 13785849 423872 uroπyl 2-suIfotransferase AB020316 Hs 134015 44 185918606202 424874 Homo sapiens cDNA FLJ20812 fis, clone A AA347951 Hs 326413 44 20156309 451460 ESTs AI797550 Hs 209652 44 42328087 411573 KIAA1077 protein AB029000 Hs 70823 44 5425435199 446673 LPAP for lysophosphatidic acid phosphat NM 016361 Hs 1 5871 44 386638677787 450835 hypothetical protein FLJ10767 BE262773 Hs 25584 44 41998060 450087 MUM2 protein BE293180 Hs 24379 44 41338008 446522 putative receptor protein NMJ03876 Hs 1 5196 44 385038517773 409799 phosphoseπne phosphatase like D11928 Hs 76845 44 3875081 416737 LIM domain protein AF154335 Hs 79691 44 102810295582 422949 gb EST21657 Adrenal gland tumor Homo sa AA319435 Hs 283435 44 17616129 443114 ESTs AI033377 Hs 368631 44 36027569 458629 Homo sapiens cDNA FLJ13565 fis, clone P AW373104 Hs 25094 44 45778374 436396 wingless type MMTV integration site fam AI683487 Hs 152213 44 31847189 415906 Homo sapiens cDNA FLJ22256 fis, clone AI751357 Hs 288741 44 9565526 414931 Homo sapiens mRNA, cDNA DKFZp761M0223 AK000342 Hs 77646 44 8918925475 418836 ESTs AI655499 H Hss 116611771122 4 444 12765771 413278 interferon stimulated protein, 15 kDa BE563085 Hs 833 44 6955322 400292 NAME OMITTED receptor kinase AA250737 Hs 72472 44 54616 425139 protease, serine, 23 AW630488 Hs 25338 44 20546338 423332 sorting nex 7 AI091466 Hs 127241 44 17956155 443105 chondroitm sulfate proteoglycan 4 (met X96753 Hs 9004 44 360036017568 441297 ubiquitm conjugating enzyme E2E 1 (hom AW403084 Hs 7766 44 35087483 424834 Homo sapiens cDNA FLJ10570 fis, clone N AK001432 Hs 153408 44 20096304 422573 integrin, alpha V (vitronectin recepto AW297985 Hs 295726 44 17046088 447200 Homo sapiens cDNA FLJ14028 fis, clone H BE543146 Hs 281434 44 38997815 438640 low density lipoprotein receptor-relate AB017498 Hs 6347 44 334333447329 454024 hypothetical protein FLJ23403 AA993527 Hs 293907 44 44818290 456940 ESTs H46986 Hs 31861 44 45348336 409124 N-acetylglucosamimdase, alpha- (Sanfil AW292809 Hs 50727 44 3075023 438274 ESTs A1918906 Hs 55080 44 3313 7304 417819 ESTs AI253112 Hs 133540 44 1160 5683 413020 gb yr31 h09 r1 Soares fetal liver spleen R98736 44 670 5303 419086 Kallmanπ syndrome 1 sequence NM 000216 Hs 89591 44 1300 1301 5789 433075 sortilm 1 NMJ02959 Hs 351872 44 293629376987 452461 transcription factor N78223 Hs 108106 44 4333 8167 445547 gatactosylceramidase (Krabbe disease) D86181 Hs 273 43 378237837717 444838 ESTs AV651680 Hs 208558 43 3728 7675 414416 hypothetical protein MGC2721 AW409985 Hs 76084 43 813 5417 408449 dyna in 1 NM 004408 Hs 1 66161 43 2242254958 425289 interferon, gamma inducible protein 16 AW139342 Hs 155530 43 2082 6358 426265 ESTs AA421069 Hs 97896 43 2189 6432 450222 TATA box binding protein (TBP)-assocιat U75308 Hs 24644 43 414341448016 450385 synuclem, alpha interacting protein (s A1631024 Hs 24948 43 4162 8030 416498 potassium channel, subfamily K, member U33632 Hs 79351 43 1007 1008 5568 410268 six transmembrane epithelial antigen of AA316181 Hs 61635 43 441 5120 438913 ESTs AI380429 Hs 172445 43 3364 7347 410055 gene forseπne/threoπine protein kinas AJ250839 Hs 58241 43 4144155102 430547 diacylglycerol kinase, iota NM 004717 Hs 242947 43 270727086811 430030 lectin, galactoside-biπding, soluble, 1 BE300094 Hs 227751 43 2641 6764 406627 ESTs T64904 Hs 163780 43 30 4812 450001 solute carrier family 6 (neurotransmitt NM 001044 Hs 406 43 412741288004 427578 ESTs, Highly similar to TUL3 HUMAN TUBB AI591305 Hs 169084 43 2347 6541 417791 ESTs AW965339 Hs 44269 43 1158 5681 426250 Homo sapiens cDNA FLJ11752 fis, clone H BE243154 Hs 183702 43 2188 6431 409893 minichromosome maintenance deficient (S AW247090 Hs 57101 43 397 5088 403908 Autosomal Highly Conserved Protein 43 4733 426316 meningioma (disrupted in balanced trans NM 002430 Hs 268515 43 220322046441 439402 ESTs W02753 Hs 103002 43 33957378 410275 transcription factor AP-2 gamma (activa U85658 Hs 61796 43 4454465123 421802 Homo sapiens, Similar to CGI-78 protein BE261458 Hs 108408 43 15956007 426365 RNA binding motif protein 8B AA376667 Hs 380056 43 22126447 426207 HSPC182 protein BE390657 Hs 30026 43 21866429 433036 ESTs AA574091 Hs 105964 43 29296981 416640 neuron-specific protein BE262478 Hs 13406 43 10195576 412723 hypothetical protein AF301222 AA648459 Hs 335951 43 6345271 446548 ESTs AI769392 Hs 200215 43 38567777 422526 ESTs AA311763 Hs 131056 43 16956081 422656 LIM homeobox protein 2 AI870435 Hs 1569 43 17226101 452223 hypothetical protein MGC2827 AA425467 Hs 8035 43 43028142 433800 lung type I cell membrane-associated A1034361 Hs 135150 43 30047040 408447 Homo sapiens cDNA FLJ11227 fis, clone P AK002089 Hs 45080 43 2234957 411408 calcium channel, voltage dependent, L t U76666 Hs 69949 43 5345355192 416072 growth associated protein 43 AL110370 Hs 79000 43 9695537 425580 galanm L11144 Hs 1907 43 211821196382 443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 43 36567617 424084 hypothetical protein FLJ23056 AI940675 Hs 20914 43 18956226 422828 prion protein 2 (dublet) AL133396 Hs 348821 43 174417456117 435523 membrane-spanning 4-domaιns, subfamily T62849 Hs 11090 43 31317147 409956 inhibm, beta A (activm A, activm AB AW103364 Hs 727 43 4005091 432787 HSPC054 protein NM.014152 Hs 278946 43 290529066962 422168 S100 calcium binding protein A7 (psona AA586894 Hs 112408 43 16546050 439165 KCNQ1 overlapping transcript 1 AA029517 Hs 95162 43 33797362 406431 NM_024867* Homo sapiens hypothetical pr 43 4806 422609 sialidase 1 (lysosomal sialidase) Z46023 Hs 118721 43 17116093 435256 cytokine like protein C17 AF193766 Hs 13872 43 311631177133 435520 HNOEL-iso protein AA297990 Hs 9315 43 31307146 453876 ESTs Weakly similar to I38022 hypothet AW021748 Hs 110406 43 44578271 451752 KIAA1171 protein AB032997 Hs 353087 43 425242538102 410188 hypothetical protein DKFZp586H0623 AL096739 Hs 107260 43 4294305113 416283 vascular endothelial growth factor C NM_005429 Hs 7 9141 43 9859865551 416065 proliferating cell nuclear antigen BE267931 Hs 78996 43 9685536 408331 dual specificity phosphatase 12 NM..007240 Hs 44229 43 2112124948 438337 hypothetical protein FLJ11196 AK002058 Hs 6166 43 331733187308 429687 nucleoponn 153kD AI675749 Hs 211608 43 26056737 453085 K1AA0251 protein AW954243 Hs 351573 43 43908216 411943 ESTs, Weakly similar to S44608 C02F56 BE502436 Hs 7962 43 5625214 430299 serine carboxypeptidase 1 precursor pro W28673 Hs 106747 43 26786792 435461 ESTs AI075846 Hs 133996 43 31277143 423032 RAS p21 protein activator (GTPase activ AI684746 Hs 119274 43 1771 6137 421079 NCK adaptor protein 2 AW404994 Hs 101695 43 15045943 412652 ESTs AI801777 Hs 352554 43 6265264 418102 hypothetical protein MGC15880 R58958 Hs 26608 43 11925709 422938 centromere protein A (17kD) NM_001809 Hs 1594 43 175917606128 428305 cartilage linking protein 1 AA446628 Hs 2799 43 24266607 432241 KIAA1151 protein AI937060 Hs 6298 43 28586922 433969 ESTs, Weakly similar to PC4395 mucm 3 AW207279 Hs 271786 43 30207053 441224 calumenin AU076964 Hs 7753 43 35047479 435472 triggering receptor expressed on myeloi AW972330 Hs 283022 43 31297145 413672 gb QV0-HT0368 310100 091-MO HT0368 Hom BE156536 Hs 35363243 7375353 410552 fibroblast growth factor receptor 1 (fm X66945 Hs 748 43 4744755144 448775 nudix (nucleoside diphosphate linked mo AB025237 Hs 388 43 403640377927 435837 Homo sapιens cDNA FLJ11431 fis, cloπe H AI689210 Hs 187276 4 2 31567165 452698 chemokme (C-C motif) receptor 1 NM J01295 Hs 3 01921 42 434343448177 431825 ESTs AI983564 Hs 292917 42 28266899 409021 fatty acid binding protein 3 muscle an AA156640 Hs 49881 42 2955014 453905 LIM domain kinase 1 NM 002314 Hs 36566 42 446244638276
450414 KIAA1716 protein AI907735 Hs 21446 42 4165 8033
440105 Homo sapiens clone 23809 mRNA sequence AA894010 Hs 6932 42 3455 7435
435142 ESTs A1051967 Hs 110122 42 3109 7127
446006 deafness, autosomal dominant 5 NM_004403 Hs 1 3530 42 380838097738
447674 cyclin dependent kinase 2 BE270640 Hs 19192 42 3947 7854
413821 ESTs, Weakly similar to C4HU complement AA844126 Hs 55964 42 746 5361
453910 Kruppel-like zinc finger protein GLIS2 AL133794 Hs 16313 42 4464 8277
416137 ubiquitm activating enzyme E1-lιke pro BE279513 Hs 278607 42 977 5544
407116 ESTs AA1309B6 Hs 271627 42 112 4864
417387 ESTs AW021102 Hs 21509 42 1108 5646
412719 ESTs AW016610 Hs 816 42 633 5270
444001 ESTs, Moderately similarto S65657 alph AI095087 Hs 152299 42 3667 7626
443351 Homo sapiens cDNA FLJ13471 fis, clone P AW016783 Hs 30799 42 3617 7583
432235 ESTs AA531129 Hs 190297 42 2855 6920
429978 nbosomal protein S6 AA249027 Hs 353161 42 2629 6757
401621 NM_025193 Homo sapiens 3 beta hydroxy-d 42 4656
415321 ESTs, Weakly similar to A47582 B cell g R54203 Hs 268723 42 922 5498
436449 ESTs AI418027 Hs 120361 42 3189 7194
416860 actin filament associated protein D25248 Hs 80306 42 1043 5593
411089 cell division cycle 2-lιke 1 (PITSLRE p AA456454 Hs 214291 42 513 5173
403903 C5001632*gι|10645308|gb|AAG214301|AC0 42 4731
420834 ESTs AA837124 Hs 88780 42 1484 5928
453754 ESTs AW972580 Hs 172753 42 4438 8257
431350 ESTs AI192528 Hs 164537 42 2775 6860
452056 Homo sapiens, clone IMAGE 4054156, mRNA AW955065 Hs 10115042 4280 8123
412014 ESTs, Weakly similar to A46010 X-linked AI620650 Hs 43761 42 566 5218
438867 opiate receptor-like 1 AW451157 Hs 2859 42 3362 7345
448684 hypothetical protein FLJ13390 similar t AA923142 Hs 24884 42 4026 7918
450066 ESTs, Weakly similar to I38022 hypothet H56499 Hs 252692 42 4132 8007
407792 putative secreted ligand homologous to AI077715 Hs 39384 42 162 4906
448103 hypothetical protein FLJ11362 AA968672 Hs 8929 42 3976 7878
414152 thrombospondm 4 NM_003248 Hs 75774 42 7827835391
422766 heparan sulfate (glucosamine) 3-O-sulfo AA33410B Hs 159572 42 1735 6111
414178 ESTs, Weakly similar to I38022 hypothet AW957372 Hs 46791 42 788 5396
426890 ESTs AA393167 Hs 41294 42 2283 6494
421814 thrombospondm 2 L12350 Hs 108623 42 1596 15976008
435906 SAR1 protein AI686379 Hs 110796 42 3161 7169
438461 phosphoseπne aminotransferase AW075485 Hs 286049 42 3326 7316
439706 ESTs, Weakly similar to DAP1_HUMAN DEAT AW872527 Hs 59761 42 3421 7404
418117 linker for activation of T cells AI922013 Hs 83496 42 1195 5712
439815 hypothetical protein FLJ20420 AA206079 Hs 6693 42 3433 7416
419271 ESTs N34901 Hs 348603 42 1324 5808
451691 ESTs AI809278 Hs 208152 42 4248 8099
420900 ESTs AL045633 Hs 44269 42 1490 5933
440524 ESTs R71264 Hs 16798 42 3474 7452
431988 protein kinase C beta 1 AC002302 Hs 349845 42 2837 6906
412580 similar to CABLES [Homo sapiens] AA113262 Hs 17901 42 610 5253
457313 transcriptional coactivator AF047002 Hs 241520 42 454445458345
416361 ESTs, Weakly similar to CA13_HUMAN COLL AW204907 Hs 6872 42 995 5558
425077 synovial sarcoma translocaton gene on AB014593 Hs 154429 42 204620476332
413945 CD14 antigen NMJ00591 Hs 75627 42 7587596371
427790 hypothetical protein MGC8641 NM_002887 Hs 1 80832 42 236923706560
453931 ESTs AL121278 Hs 25144 42 4469 8280
431410 ESTs AW299534 Hs 105739 42 2781 6865
410512 hypothetical protein MGC3180 AA085603 Hs 250570 42 468 5140
447726 matπlin 2 AL137638 Hs 19368 41 395339547859
434826 pyruvate dehydrogenase phosphatase AF155661 Hs 22265 41 307830797101
402685 Target Exon 41 4687
440028 ESTs, Weakly similar to T17227 hypothet AW473675 Hs 367649 41 3446 7428
428418 ESTs AI368826 Hs 8768 41 2441 6619
416404 ESTs AA180138 Hs 107924 41 1000 5563
435181 KIAA1571 protein AA669339 Hs 28838 41 3112 7130
442767 ESTs A1017208 Hs 131149 41 3584 7552
427528 minichromosome maintenance deficient (S AU077143 Hs 179565 41 2341 6537
456327 ESTs H68741 Hs 38774 41 4518 8322
437763 tissue inhibitor of metalloproteinase 1 AA469369 Hs 5831 41 3285 7278
458823 ESTs AW207574 Hs 179501 41 4581 8378
458997 ESTs AW937420 Hs 351869 41 4588 8384
444207 cathepsm D (lysosomal aspartyl proteas AI565004 Hs 374415 41 3686 7643
415812 TATA box binding protein (TBP)-assocιat AA077268 Hs 78865 4 1 949 5521
416823 ESTs N68454 Hs 16222 41 1037 5588
414907 polo (Drosophia) like kinase X90725 Hs 77597 41 886 8875472
438454 ESTs AI377324 Hs 136888 41 3324 7314
432435 ESTs BE218886 Hs 282070 41 2874 6936
428344 Homo sapiens cDNA FLJ12425 fis, clone M AW449466 Hs 9299 41 2433 6612
432106 ESTs, Weakly similar to RETROVIRUS-RELA N58323 Hs 269098 41 2842 6910
408705 HSPC034 protein AA312135 Hs 46967 41 250 4980
409702 eukaryotic translation elongation facto A1752244 Hs 351558 41 380 5075
412802 aquapoππ 1 (channel-forming integral p U41518 Hs 74602 41 6456465282
434095 milk fat globule EGF factor 8 protein ( AA011117 Hs 3745 41 3028 7061
420303 KIAA1474 protein AA258282 Hs 278436 41 1443 5900
425207 Homo sapiens, clone MGC 3182, mRNA , com AB014551 Hs 337774 4 1 2065 20666346
448569 signal transducer and activator of tran BE382657 Hs 21486 41 4014 7909
431882 engrailed homolog 1 NM_001426 Hs 271977 4 1 2832 28336903
437673 ESTs AW665665 Hs 153034 41 3279 7272 405203 NM-002086* Homo sapiens growth factor r 41 4772 428825 ESTs, Weakly similar to I38022 hypothet AI084336 Hs 128783 41 24786646 425966 cyclin F NMJJ01761 Hs 1 973 41 215821596409 439496 Homo sapiens, Similarto RIKEN cDNA 111 BE616501 Hs 32343 41 34027385 443715 cyclin E1 A1583187 Hs 9700 41 36387601 417426 lamimn, beta 1 NM-.002291 Hs 8 2124 41 111911205654 416292 nasopharyngeal carcinoma susceptibility AA179233 Hs 42390 41 9875552 415107 gb HUM089A11B Clontech human fetal brai D60154 41 9095488 443950 epithelial membrane protein 3 NM_001425 Hs 9 999 41 366036617621 426413 gb EST90805 Synovial sarcoma Homo sapie AA377823 41 22196453 418514 TOLLIP protein AW068487 Hs 25413 41 12485749 414110 gb 601112444F1 NIH_MGC_16 Homo sapiens BE251752 41 7765385 444024 ESTs AW205686 Hs 348603 41 36717630 457396 DKFZP547E1010 protein Z20964 Hs 323817 41 45468346 408932 TP53TG3 protein AW594172 Hs 278513 41 2775000 458806 Homo sapiens PNAS 13 mRNA, complete eds BE514753 Hs 29205741 45808377 447898 62 kd protein AW969638 Hs 380920 41 39667868 412530 hypothetical protein FLJ13346 AA766268 Hs 266273 41 6005246 439452 B cell CLUIymphoma 11B (zinc finger pr AA918317 Hs 57987 41 33987381 442328 ESTs, Weakly similar to ALU4.HUMAN ALU AI952430 Hs 150614 41 35567528 425133 3-phosphoιnosιtιde dependent protein ki NMJ02613 Hs 1 54729 41 205220536337 432539 karyopheπn beta 2b, traπsportin AL138169 Hs 278378 41 28856946 433446 ESTs AW469546 Hs 122116 41 29797020 449611 ESTs AI970394 Hs 197075 41 41007981 425354 complement component 3a receptor 1 U62027 Hs 155935 41 209320946365 439453 thyroid hormone receptor interactor 13 BE264974 Hs 6566 41 33997382 422320 ESTs, Weakly similar to AAB47496 NG5 [H AI745249 Hs 23650 41 1671 6063 449475 hypothetical protein PP1057 AI348027 Hs 129826 41 40917973 413950 ESTs NB B AA249096 Hs 32793 41 7605372 430071 transcπption factor 8 (represses inter AA355986 Hs 380991 41 26486770 453708 ESTs AI191811 Hs 54629 41 44358254 400263 Eos Control Hs 75309 41 4613 443402 elastm (supravalvular aortic stenosis, U77846 Hs 9295 41 361936207585 407065 gb H sapiens DAT1 gene, partial, VNTR Y10141 41 1031044857 404063 Target Exon 41 4737 433932 neuronal protein AW954599 Hs 169330 41 30177051 419081 ESTs AI798863 Hs 87191 41 12995788 447072 tyrosylprotein sulfotraπsferase 1 D61594 Hs 17279 41 38877804 445413 CGI-147 protein AA151342 Hs 12677 41 37657704 439727 Homo sapiens clone 23645 mRNA sequence R25060 Hs 6651 41 34247407 432222 gb an03c03 x1 Stratagene schizo brain S AI204995 41 45966919 408915 heptacellular carcinoma novel gene-3 pr NM 016651 Hs 48950 41 2742754998 417687 ESTs AI828596 Hs 250691 41 11475672 453271 ESTs AA903424 Hs 6786 41 44098232 443595 PPARfgamma) angiopoietm related protei AF169312 Hs 9613 41 362636277590 413658 A kinase (PRKA) anchor protein 10 AA055369 Hs 372446 41 7345351 401176 Target Exon 41 4646 428976 ras homolog gene family, member I AL037824 Hs 194695 41 24956658 441831 PR domain containing 16 AA992586 Hs 302022 41 35387510 414280 zyxm BE410769 Hs 75873 41 7965403 404632 NMJJ22490 Homo sapiens hypothetical pro 41 4754 449263 NICE-5 protein BE560779 Hs 337078 40 40767958 407688 Human D9 splice variant B mRNA, complet W25317 Hs 37616 40 1494894 408513 ESTs AW206468 Hs 103118 40 2344965 437980 KIAA1474 protein R50393 Hs 278436 40 32957288 412326 small inducible cytokine A3 (homologous R07566 Hs 73817 40 5825231 410577 glioma pathogenesis related protein X91911 Hs 64639 40 4764775145 428206 KIAA0836 protein AB020643 Hs 183006 40 240524066590 448743 KIAA1136 protein AB032962 Hs 21896 40 403240337924 416062 Homo sapiens cDNA FLJ14609 fis, clone N AA724811 Hs 334791 40 9675535 445252 Homo sapiens clone 23927 mRNA sequence AF052109 Hs 12473 40 37527695 428579 G protein coupled receptor 64 NM_005756 Hs 1 84942 40 245424556628 433221 KIAA1484 protein AB040917 Hs 97860 40 295829597003 427584 v-myb avian myeloblastosis viral oncoge BE410293 Hs 179718 40 23486542 441648 ESTs H05734 Hs 30559 40 35317503 407907 procollagen lysine, 2-oxoglutarate 5 di AI752235 Hs 41270 40 1794921 414175 hypothetical protein DKFZp761 D112 AI308876 Hs 103849 40 7865394 419326 ESTs W94915 Hs 42419 40 13295812 459247 ESTs, Highly similar to T42626 secreted N46243 Hs 110373 40 45908386 438685 ESTs AA814034 Hs 146065 40 33477332 440080 ESTs AW051597 Hs 143707 40 34497431 419222 spermme synthase AD001528 Hs 89718 40 131813195803 426340 FYN oncogene related to SRC, FGR, YES Z97989 Hs 169370 40 22086444 424365 ESTs, Moderately similar to I54374 gene AI653164 Hs 128665 40 19386255 428412 ESTs AA428240 Hs 126083 40 24406618 407566 Homo sapiens cDNA FLJ12280 fis, clone M AW068805 Hs 288467 40 1424888 419574 hypothetical protein AK001989 Hs 91165 40 135313545830 445893 ESTs, Weakly similar to TRHYJHUMAN TRIC AI610702 Hs 202613 40 38027732 423811 homeo box C4 AW299598 Hs 50895 40 18546198 447818 Homo sapiens clone 24670 mRNA sequence W79940 Hs 355279 40 39657867 400231 Eos Control Hs 169476 40 4603 451598 ESTs N29102 Hs 79658 40 42418093 408482 adenosine A2b receptor NM_000676 Hs 45743 40 2262274959 425741 Homo sapiens clone 24628 mRNA sequence AF052152 Hs 129997 40 21336391 446254 Homo sapiens cDNA FLJ12832 fis, clone N BE179829 Hs 179852 40 38307757 442410 ESTs AW996503 Hs 197680 40 35597531 408433 ras related C3 botulmum toxin substrat AW162931 Hs 45002 40 221 4955 445809 phosphoπbosyl pyrophosphate synthetase AA295298 Hs 13339 40 3799 7729 409698 short stature homeobox 2 AF022654 Hs 55967 40 3783795074
TABLE 9B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
459702 539529 1 BG207209 BE166299 AI204995 BG199355A 969908 AA528756 AW440776 BI044354
458956 81880J BE873716 BE907282AA009992 BE220675 AA345621
415179 1863582 1 D80630 D80896 D80895
459674 118159J AW974566 AA649022 BF740489 BF930101 BF930097 BF930102 AA180511
439579 24302.1 AF086400 W73990 W79232
439195 21979 1 AF086037 H89360 H89546
429163 1238297 AW974271 AA592975 AA447312AA884766
411962 2307710J AA099050 AA099526 T47733
413020 1485885 1 BE048113 R98736 Z42904
415107 1856205 1 D61323 D60154 D81503 D81360 D60938 D60422 D60251 D81628 D60135
426413 372468 ϊ A 954494 AA377823 BG21961 BG195685 BG616269 AI022688
414110 1634167 1 BE253764 BE250764 BE255757 BE251752 BE251925
432222 539529J BG207209 BE166299 AI204995 BG199355 AW969908 AA528756 AW440776 BI044354
TABLE 9C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers Dunham I et al ' refers to the publication entitled
"The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489495 Strand Indicates DNA strand from which exons were predicted
NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
404977 3738341 Minus 43081-43229
404550 6716010 Plus 190794-192418
403171 9838164 Minus 74502-74703
403907 7710682 Minus 61974-62176,62689 62996 404815 5911819 Minus 64494-64691
402992 7767907 Minus 42137-42515
401797 6730720 Plus 6973-7118
401131 8699812 Minus 94802-94987,95804-95887,96323-96487,9759
402855 9662953 Minus 59763-59909
404245 7406725 Plus 36019-36282,37073 37813,38946-39314,4035
401130 8699792 Plus 121013-121360
402233 7690102 Plus 90281-91477
402507 9797889 Plus 118979-119086
403909 7710682 Minus 64580 6465867678 67795
400615 9908994 Plus 118036-118166,118681-118807
405267 1841544 Plus 72660-72983,78939-79262,82269 82601,8448
402812 6010110 Plus 25026-25091,25844-25920
402794 6136940 Minus 131034-131794
402888 9930892 Minus 54727-54901
403857 7708910 Minus 2524-3408
402408 9796239 Minus 110326-110491
404913 7341740 Plus 97717-97976
403908 7710682 Minus 63947-64187 406431 9256478 Minus 105179 105408 401621 8570184 Minus 193-608 403903 7710671 Minus 101165-102597 402685 8318556 Plus 58962-59294 405203 7230116 Plus 125295-125463 404063 3540156 Minus 55360-57603 401176 9438469 Minus 20475-20734 404632 9796668 Plus 45096 45229
TABLE 10A
Pkey Unique Eos probeset identifier number
Gene name Unigene gene title
Accession Exemplar Accession number, Genbank accession number
UniGene Unigene number
RATIO 95th percentile of soft tissue sarcoma AIs divided by the 50th percentile of normal soft tissue AIs, where the 10th percentile of normal tissue AIs was subtracted from both the numerator and denominator
SEQ ID # nucleic acid and protein sequences provided on CD for search purposes
Pkey Gene Name A Acccceessssiioonn UniGene RATIO SEQ ID #
426752 titin X X6699449900 Hs 172004 20 8 226622676482
400440 nebul X X8833995577 Hs 83870 178 24254627
417070 titin Z Z1199007777 Hs 172004 166 1070 5614
407013 gb Human nebulm mRNA, partial eds U U3355663377 Hs 83870 162 94954851
406704 myosin, heavy polypeptide 7, cardiac mu M M2211666655 Hs 929 146 55564826
417866 collagen, type XI, alpha 1 A AWW0066779900:3 Hs 82772 138 1162 5685
417389 idkine (neuπte growth promoting facto B BEE226600996644 Hs 82045 130 1109 5647
410621 titin A AAA119944332299 Hs 172004 123 481 5149 444381 hypothetical protein BC014245 BE387335 Hs 283713 120 3697 7652
432874 melanoma inhibitory activity W94322 Hs 279651 11 3 2913 6968
418054 lysyl oxidase-like 2 NM..002318 Hs 83354 11 3 118411855702
405001 interleukin enhancer binding factor 1 11 3 4767
428405 cholinergic receptor, nicotimc, alpha Y00762 Hs 2266 11 1 243624376615
414482 endothelm receptor type A S57498 Hs 76252 11 0 8248255426
410687 lysyl oxidase-like 1 U24389 Hs 65436 104 4854865153
413011 biglycaπ AW068115 Hs 821 103 669 5302
422311 cytokine receptor-like factor 1 AF073515 Hs 114948 100 1669 16706062
409633 ESTs AW449822 Hs 55200 99 371 5068
411296 growth suppressor 1 BE207307 Hs 10114 94 524 5183
438089 nuclear receptor subfamily 1 , group 1, W05391 Hs 351546 88 3301 7294
403088 NM..003319* Homo sapiens titin (TTN), i mR 87 4707
422069 titin cap (telethon ) AJ010063 Hs 343603 87 1635 16366037
443426 chromosome 20 open reading frame 1 AF098158 Hs9329 84 3621 36227586
438091 nuclear receptor subfamily 1, group I, AW373062 Hs 351546 83 3302 7295
413566 sprouty (Drosophila) homolog 4 AW604451 Hs 381153 83 730 5347
413278 interferon-stimulated protein, 15 kDa BE563085 Hs 833 82 695 5322
414821 Fc fragment of IgG, high affinity la, r M63835 Hs 77424 82 8768775465
425397 topoisomerase (DNA) II alpha (170kD) J04088 Hs 156346 82 209921006369
423778 flavin containing monooxygenase 2 Y09267 Hs 132821 82 1846 18476193
418506 Unknown protein for MGC 29643 (formerly AA084248 Hs 372651 81 1247 5748
429259 Plakophilm AA420450 Hs 380088 80 2535 6689
438746 Human melanoma associated antigen p97 AI885815 Hs 184727 79 3353 7337
435523 membrane spanning 4domaιπs, subfamily T62849 Hs 11090 78 3131 7147
422627 transforming growth factor, beta induce BE336857 Hs 118787 77 1715 6097
414812 monokme induced by gamma interferon X72755 Hs 7367 76 8748755464
427747 seπne/threonine kinase 12 AW411425 Hs 180655 76 2365 6557
444006 type I transmembrane protein Fn14 BE395085 Hs 334762 76 3668 7627
432481 intron of collagen, type XI, alpha 1 AW451645 Hs 151504 75 2876 6938
421143 immunoglobulin superfamily containing I AB024536 Hs 102171 75 1510 1511 5949
452701 glutamine-fructose 6 phosphate transami NM_005110 Hs 30332 75 434543468178
451099 interleukin 13 receptor, alpha 2 R52795 Hs 26954 75 4212 8071
425308 receptor tyrosine kinase like orphan re M97639 Hs 155585 75 208720886362
409142 SMC4 (structural maintenance of chromos AL136877 Hs 50758 74 3123135027
428981 ESTs, Weakly similar to ALU2_HUMAN ALU BE313077 Hs 93135 73 2497 6660
415166 carboxypeptidase Z NMJ03652 Hs 78068 73 913 9145491
452683 progesterone membrane binding protein AI089575 Hs 374574 73 4341 8175
414443 platelet-derived growth factor receptor AU077268 Hs 76144 73 817 5421
423217 collagen, type VII alpha 1 (epidermoly NM 000094 Hs 1 640 72 178417856147
421508 absent in melanoma 2 NM 004833 Hs 1 05115 7 1 1551 15525977
450447 hypothetical protein P15-2 AF212223 Hs 25010 70 416841698036
424162 ESTs, Weakly similar to ALU2_HUMAN ALU AA336229 Hs 93135 70 1907 6235
446051 ephπn-A3 BE048061 Hs 37054 70 3816 7744
407792 putative secreted ligand homologous to AI077715 Hs 39384 69 162 4906
400499 C10001858 gι|6679124|ref|NP_032759 1| n 69 4628
437206 ESTs, Weakly similar to 138344 titin, c AW975934 Hs 172004 68 3245 7242
451766 ephnn-B3 NM 001406 Hs 26988 68 425542568104
418478 cyclm-dependent kinase inhibitor 2A (m U38945 Hs 1174 68 1245 12465747
433577 ESTs AW007080 Hs 284192 68 2989 7028
418203 CDC28 protein kinase 2 X54942 Hε 83758 68 120212035719
427337 Fc fragment of IgG, low affinity lllb, Z46223 Hs 176663 67 231823196521
409012 DKFZP434I216 protein AL117435 Hs 49725 66 2932945013
444784 ectonucleotide pyrophosphatase/phosphod D12485 Hs 11951 66 372437257673
431183 KDEL (Lys-Asp-Glu Leu) eπdoplasmic reti NM 006855 : Hs 250696 65 275627576845
448672 ESTs AI955511 Hs 89582 65 4025 7917
433075 sortilin 1 NM 002959 Hs 351872 64 293629376987
448390 hypothetical protein AL035414 Hs 21068 64 3999 7897
413436 sphingosme kinase 1 AF238083 Hs 68061 64 721 7225339
434149 hypothetical protein MGC5469 Z43829 Hs 244624 64 3030 7063
452363 Homo sapiens Similar to complement com AI582743 Hs 94953 63 4322 8159
424870 ESTs T15545 Hs 244624 63 2014 6308
439285 hypothetical protein FLJ20093 AL133916 Hs 47860 63 3389 7372
422667 ESTs H25642 Hs 132821 63 1723 6102
448520 doublecortm and CaM kinase like 1 AB002367 Hs 21355 63 40104011 7907
452291 CDC7 (cell division cycle 7, S cerevis AF015592 Hs 28853 63 43104311 8150
417355 endothelm receptor type B D13168 Hs 82002 63 1100 1101 5640
427418 LAT1-3TM protein AA402587 Hs 356667 63 2327 6527
437696 hypothetical protein dJ37E165 Z83844 Hs 6790 62 3281 7274
428450 KIAA0175 gene product NM 014791 Hs 1 84339 62 244324446621
426457 chimerm (chimaenn) 1 AW894667 Hs 380138 61 2229 6459
448595 KIAA0644 gene product AB014544 Hs 21572 61 401540167910
418322 cyclin dependent kinase inhibitor 3 (CD AA284166 Hs 84113 60 1214 5727
429903 cyclin dependent kinase 5, regulatory s AL134197 Hs 93597 60 2616 6746
408938 ESTs AA059013 Hs 22607 60 279 5002
417079 interleukin 1 receptor antagonist U65590 Hs 81134 60 1073 10745616
413795 ESTs AL040178 Hs 142003 60 743 5358
443907 TYRO protein tyrosine kinase binding pr AU076484 Hs 9963 59 3656 7617
456534 phospholipase C, beta 3, neighbor pseud X91195 Hs 100623 59 4522 8326
420162 cyclin dependent kinase 4 BE378432 Hs 95577 58 1422 5883
447217 neuropilm 2 BE465754 Hs 17778 58 3904 7819
419138 ryaπodine receptor 1 (skeletal) U48508 Hs 89631 58 130913105796
427378 melanoma antigen family D, 1 BE515037 Hs 177556 58 2322 6523
424263 L1 cell adhesion molecule (hydrocephalu M77640 Hs 1757 58 1925 19266246
439668 frizzled (Drosophila) homolog 8 AI091277 Hs 302634 58 3414 7397
412507 EphA4 L36645 Hs 73964 57 596 5975243 429921 collagen, type XI, alpha 1 AA526911 Hs 82772 57 2620 6749
414555 phospholipase A2, group IIA (platelets, N98569 Hs 76422 57 830 5431
426968 amphiphysm (Stiff-Mann syndrome with b U07616 Hs 173034 57 22902291 6499
411021 titin F00055 Hs 172004 57 508 5169
424829 nerve growth factor receptor (TNFR sup. i NM 002507 Hs 1 827 57 200720086303
411089 cell division cycle 2-lιke 1 (PITSLRE p AA456454 Hs 214291 56 513 5173
435905 KIAA0456 protein AW997484 Hs 5003 56 3160 7168
447343 ESTs, Highly similar to S02392 alphas- AA256641 Hs 236894 56 3916 7828
400263 Eos Control Hs 75309 56 4613
418299 integrin, beta 2 (antigen CD18 (p95), 1 AA279530 Hs 83968 55 1212 5725
448961 ESTs AI610643 Hs 187285 55 4052 7937
429170 dual specificity phosphatase 4 NM 001394 Hs 2359 55 252425256680
404815 ENSP00000251989* DJ100N22 1 (NOVEL EGF- 55 4761
425262 GS3955 protein D87119 Hs 155418 55 2076 20776354
421506 thymidine kinase 1, soluble BE302796 Hs 105097 55 1550 5976
439039 ESTs AI656707 Hs 48713 55 3373 7356
432994 ESTs AA573452 Hs 150941 55 2922 6976
418004 aldehyde dehydrogenase 3 family, member U37519 Hs 87539 55 1174 11755695
410223 calsequestπn 1 (fast-twitch, skeletal S73775 Hs 60708 55 4334345115
422765 baculoviral IAP repeat containing 5 (su AW409701 Hs 1578 55 1734 6110
451598 ESTs N29102 Hs 79658 55 4241 8093
424078 paternally expressed 3 AB006625 Hs 139033 55 1893 1894 6225
400288 integrin alpha 5 (fibronectin receptor X06256 Hs 149609 54 1 24614
416491 parathyroid hormone receptor 1 U17418 Hs 1019 54 1005 10065567
452698 chemokine (C-C motif) receptor 1 NM 001295 Hs 3 01921 54 434343448177
451292 KIAA1295 protein AB037716 Hs 26204 54 4221 42228079
454071 ESTs A1041793 Hs 42502 54 4487 8295
410011 PFTAIRE protein kinase 1 AB020641 Hs 57856 54 4064075096
412939 eukaryotic translation elongation facto AW411491 Hs 75069 53 657 5292
432691 mitogen activated protein kinase 7 U29725 Hs 3080 53 28972898 6956
448569 signal transducer and activator of tran BE382657 Hs 21486 53 , 4014 7909
414477 amplified in osteosarcoma U41635 Hs 76228 53 8228235425
416140 roundabout (axon guidance receptor, Dro AI918035 Hs 301198 53 978 5545
441389 endocytic receptor (macrophage mannose AF13483B Hs 835 53 351435157488
447232 interleukin 10 receptor, alpha AW499834 Hs 327 53 3905 7820
456181 ras inhibitor L36463 Hs 1030 53 451645178321
408482 adenosine A2b receptor NM 000676 Hs 45743 53 2262274959
425964 progesterone membrane binding protein AW889928 Hs 9071 52 2157 6408
421920 gamma aminobutyric acid (GABA) receptor BE551245 Hs 1438 52 1614 6022
427700 dual specificity phosphatase 6 AA262294 Hs 180383 52 2361 6554
414024 gb zm79g08 r1 Stratagene neuroepitheliu AA134712 Hs 22410 52 769 5379
443960 hypothetical protein FLJ21986 AI093577 Hs 255416 52 3663 7623
421251 enigma (LIM domain protein) Z28913 Hs 102948 52 1521 5957
419762 ESTs AI608647 Hs 32374 52 1387 5855
422175 ESTs, Highly similar to T00391 hypothet N79885 Hs 6382 52 1657 6053
426485 platelet deπved growth factor receptor NM.006207 Hs 1 70040 51 223822396465
429150 smoothened (Drosophila) homolog AF120103 Hs 197366 51 251925206677
409430 splicing factor, argmine/senne-πch 5 R21945 Hs 346735 51 348 5052
418059 gb zπ56d05 s1 Stratagene muscle 937209 AA211586 51 1186 5703
427647 Homo sapiens cDNA FLJ20653 fis, clone K W19744 Hs 180059 5 1 2354 6548
438937 ESTs AW952654 Hs 73964 51 3367 7350
449353 ESTs AA001220 Hs 242947 5 1 4084 7966
432101 EphA3 AI918950 Hs 123642 51 2841 6909
418883 acid phosphatase 5, tartrate resistant BE387036 Hs 1211 5 1 1281 5774
417115 small nuclear πboπucleoprotein polypep AW952792 Hs 334612 50 1081 5622
424291 ephrιπ-B1 AL120051 Hs 144700 50 1931 6249
435652 uncharacterized hypothalamus protein HB N32388 Hs 334370 50 3142 7154
410342 Fc fragment of IgE, high affinity 1, re R31350 Hs 743 50 453 5129
453880 ESTs, Weakly similar to 138022 hypothet AI803166 Hs 135121 50 4458 8272
419452 PTK7 protein tyrosine kinase 7 U33635 Hs 90572 50 1340 1341 5821
434431 ESTs AW131454 Hs 168571 50 3056 7082
406621 immunoglobulin lambda locus X57809 Hs 181125 50 26274810
419250 U5 snRNP-specific protein, 116 kD AW770185 Hs 356066 50 1322 5806
419073 Homo sapiens cDNA FLJ12797 fis, clone N AW372170 Hs 183918 50 1296 5786
440700 guanine nucleotide binding protein (G p AW952281 Hs 296184 50 3481 7458
417089 Homo sapiens cDNA FLJ21909 fis, clone H52280 Hs 18612 50 1077 5619
432211 hypothetical protein FLJ10986 BE274530 Hs 273333 50 2852 6917
412972 ESTs AA771898 Hs 33412 49 663 5296
414883 CDC28 protein kinase 1 AA926960 Hs 348669 49 885 5471
427557 plasminogen activator, urokinase recept NM_002659 Hs 1 79657 49 234323446539
439706 ESTs, Weakly similar to DAPLHUMAN DEAT AW872527 Hs 59761 49 3421 7404
452682 progesterone membrane binding protein AA456193 Hs 374574 49 4340 8174
446291 interferon, gamma inducible protein 30 BE397753 Hs 14623 49 3833 7760
418741 ESTs, Weakly similar to S41044 chromoso H83265 Hs 8881 49 1272 5767
448379 KIAA1130 protein A1097463 Hs 21035 49 3995 7894
447198 ESTs D61523 Hs 283435 49 3898 7814
412926 macrophage myπstoylated alanine rich C AI879076 Hs 75061 49 655 5290
411263 kinesm like 6 (mitotic centromere asso BE297802 Hs 69360 49 523 5182
407239 leukocyte immunoglobulin-like receptor, AA076350 Hs 67846 49 129 4879
439453 thyroid hormone receptor teractor 13 BE264974 Hs 6566 49 3399 7382
413031 phosphofructokmase, muscle BE515051 Hs 75160 48 671 5304
418526 solute carrier family 16 (monocarboxyli BE019020 Hs 85838 48 1251 5752
410422 Homo sapiens, clone MGC 15203, mRNA co AL042014 Hs 63348 48 462 5136
429470 guanine nucleotide binding protein (G p A1878901 Hs 203862 48 2564 6711
445930 Homo sapiens clone 24747 mRNA sequence AF055009 Hs 13456 48 3804 7734
425525 ESTs AA358883 Hs 23871 48 2111 6377 443623 complement component 1, q subcomponent, AA345519 Hs 9641 48 3631 7594
417421 nuclear receptor subfamily 4, group A, AL138201 Hs 82120 48 1118 5653
449579 ESTs, Weakly similar to T46425 hypothet AW207260 Hs 134014 48 4097 7978
450296 hepatocyte growth factor-regulated tyro AL041949 Hs 24756 48 4153 8023
453905 UM domain kinase 1 NM 002314 Hs 36566 48 44624463 8276
418532 neurotrophic tyrosine kinase, receptor, F00797 Hs 374321 48 1252 5753
443402 elastin (supravalvular aortic stenosis, U77846 Hs 9295 48 361936207585
431385 membrane-spanning 4-domaιns, subfamily BE178536 Hs 11090 48 2779 6863
425003 apuπnic/apyπmidinic endonucleasefAPEX AF119046 Hs 154149 48 203820396326
410781 ESTs AI375672 Hs 165028 48 495 5159
420261 fibroblast growth factor receptor 1 (fm AW206093 Hs 48 48 1440 5897
452110 Homo sapiens cDNA FLJ11309 fis, clone P T47667 Hs 28005 47 4290 8132
419066 PR01073 protein Z98492 Hs 203862 47 1295 5785
448386 KIAA1329 protein AB037750 Hs 21061 47 399739987896
449029 solute earner family 7 (cationic ammo N28989 Hs 22891 47 4058 7942
451752 KIAA1171 protein AB032997 Hs 353087 47 425242538102
416737 LIM domain protein AF154335 Hs 79691 47 1028 10295582
430280 interleukin 7 receptor AA361258 Hs 237868 47 2673 6787
429345 hypothetical protein R11141 Hs 199695 47 2548 6700
425514 integrin, alpha 10 AF112345 Hs 158237 47 210821096375
449523 chemokme (C-C motif) receptor 5 NM 000579 Hs 54443 47 409440957976
422599 non-metastatic cells 1, protein (NM23A) BE387202 Hs 118638 47 1710 6092
409098 pleckstππ homology, Sec7 and coiled/co AA132672 Hs 7984 47 303 5020
412641 heat shock 90kD protein 1 , beta M16660 Hs 74335 47 620621 5260
424982 phosphorylase, glycogen U94777 Hs 351580 00 203620376325
400991 Target Exon 47 4641
413441 Src like adapter AI929374 Hs 75367 47 723 5340
422609 sialidase 1 (lysosomal sialidase) Z46023 Hs 118721 46 1711 6093
424442 ESTs, Weakly similar to ZN91_HUMAN ZINC AW051949 Hs 90035 46 1954 6268
433895 mitogen-activated protein kinase kinase AI287912 Hs 3628 46 3014 7048
410711 KIAA0318 protein AB002316 Hs 65746 46 4894905155
435232 cyclin dependent kinase inhibitor 2C (p NM 001262 Hs 4854 46 311431157132
424512 integππ, beta 5 X53002 Hs 149846 46 1968 19696277
421707 lectomedιn-2 NM 014921 Hs 1 07054 46 1581 15825995
451050 ESTs AW937420 Hs 351869 46 4588 8067
447200 Homo sapiens cDNA FLJ14028 fis, clone H BE543146 Hs 281434 46 3899 7815
424503 integrin, alpha 5 (fibronectin receptor NM 002205 Hs 1 49609 46 1965 19666275
447359 adenylate kinase 5 NMJ12093 Hs 1 8268 46 391839197830
437763 tissue inhibitor of metalloproteinase 1 AA469369 Hs 5831 46 3285 7278
448775 nudix (nucleoside diphosphate linked mo AB025237 Hs 388 46 403640377927
419088 integrin, beta 8 AI538323 Hs 380684 46 1303 5791
414809 Iransferπn receptor (p90, CD71) AI434699 Hs 77356 46 873 5463
448030 membrane spanning 4-domaιns, subfamily N30714 Hs 325960 46 3971 7873
419693 FXYD domain-containing ion transport re i AA133749 Hs 301350 46 1371 5844
417098 frizzled (Drosophila) homolog 7 AB017365 Hs 173859 46 1078 10795620
414907 polo (Drosophia) like kinase X90725 Hs 77597 46 8868875472
414561 Homo sapiens ammo acid transport syste AI064813 Hs 195155 46 831 5432
400262 Eos Control Hs 75309 46 4612
428484 solute earner family 7 (cationic ammo AF104032 Hs 184601 46 244924506624
447674 cyclm-dependent kinase 2 BE270640 Hs 19192 46 3947 7854
411027 leukocyte immunoglobulm-like receptor, AF072099 Hs 67846 45 5095105170
422034 Ets2 repressor factor AC006486 Hs 333069 45 1627 16286032
447321 Homo sapiens cDNA FLJ14028 fis, clone H AW271217 Hs 281434 45 3915 7827
425741 Homo sapiens clone 24628 mRNA sequence AF052152 Hs 129997 45 2133 6391
451811 hypothetical protein MGC1136 AA663485 Hs 8719 45 4259 8106
435575 triggering receptor expressed on myeloi AF213457 Hs 44234 45 313931407152
412773 similar to vaccinia virus Hmdlll K4L 0 H15785 Hs 74573 45 639 5276
447898 62 kd protein AW969638 Hs 380920 45 3966 7868
409799 phosphoseπne phosphatase-like D11928 Hs 76845 45 387 5081
417640 protein C receptor, endothelial (EPCR) D30857 Hs 82353 45 1143 5669
416982 creatine kinase, mitochondnal 2 (sarco J05401 Hs 80691 45 105510565602
427274 colony stimulating factor 1 receptor, f NM 005211 Hs 1 74142 45 231323146517
410290 hypothetical protein DKFZp564A176 AA402307 Hs 322844 45 449 5126
413048 mannose receptor, C type 1 M93221 Hs 75182 44 6726735305
444143 ESTs, Moderately similar to A56194 thro AW747996 Hs 160999 44 3679 7637
425082 inositol 1,4,5-tnphosphate receptor, t N44238 Hs 102991 44 2048 6333
429455 CD209 antigen AI472111 Hs 278694 44 2563 6710
421917 KIAA1020 protein AB028943 Hs 109445 44 1612 16136021
445033 cyclm-dependent kinase inhibitor 2B (p AV652402 Hs 72901 44 3740 7685
452203 transporter 1, ATP-bindmg cassette, su X57522 Hs 352018 44 429842998140
446566 membrane spanning 4-domaιns, subfamily H95741 Hs 17914 44 3857 7778
409512 melanoma differentiation associated pro AW979187 Hs 293591 44 354 5057
456629 histone deacetylase 3 AW891965 Hs 367942 44 4526 8329
425776 parathyroid hormone receptor 2 U25128 Hs 159499 44 2138 21396394
439963 platelet-activating factor acetylhydrol AW247529 Hs 6793 44 3441 7423
414280 zyxm BE410769 Hs 75873 44 796 5403
451820 ESTs AW058357 Hs 199248 44 4260 8107
416084 deoxythymidylate kinase (thymidylate ki L16991 Hs 79006 43 9729735540
424905 NIMA (never in mitosis gene a) related NMJ02497 Hs 1 53704 43 20222023 6315
425770 spastic ataxia of Charlevoix-Saguenay ( NM J14363 Hs 1 59492 43 213621376393
434826 pyruvate dehydrogenase phosphatase AF155661 Hs 22265 43 3078 3079 7101
426265 ESTs AA421069 Hs 97896 43 2189 6432
410240 synaptojanm 2 AL157424 Hs 61289 43 437 5117
433028 AD 017 protein AI199144 Hs 283737 43 2928 6980
436856 ESTs AI469355 Hs 127310 43 3220 7221
407603 Homo sapiens, clone IMAGE 4299322, mRNA AW955705 Hs 62604 43 144 4890 439223 UL16 binding protein 2 AW238299 Hs 250618 43 3383 7366
425289 interferon, gamma-inducible protein 16 AW139342 Hs 155530 43 2082 6358
431429 reticulon 3 AF072813 Hs 252831 43 2783 6867
438209 aryl-hydrocarbon receptor nuclear trans AL120659 Hs 6111 43 3309 7301
410055 gene for senne/threonme protein kinas AJ250839 Hs 58241 43 4144155102
416860 actin filament associated protein D25248 Hs 80306 43 1043 5593
448988 gamma aminobutyπc acid (GABA) A recept Y09763 Hs 22785 43 405540567940
420173 ESTs AA256151 Hs 22999 43 1426 5886
408331 dual specificity phosphatase 12 NMJ07240 Hs 44229 43 211 2124948
417920 adenosine monophosphate dea inase 2 (is S47833 Hs 82927 43 1167 1168 5690
402233 NM_030760* Homo sapiens endothelial dif 43 4674
447357 ESTs AI375922 Hs 132821 43 3917 7829
408056 ephrιn-A4 AA312329 Hs 42331 43 188 4930
425322 protein kinase, DNA-activated, catalyti U63630 Hs 155637 43 208920906363
427509 complement component 5 receptor 1 (C5a M62505 Hs 2161 43 233823396535
451154 ESTs AA015879 Hs 33536 43 4215 8074
414368 uridine monophosphate kinase W70171 Hs 75939 42 809 5414
417426 lamimπ, beta 1 NM 002291 Hs 82124 42 1119 11205654
431674 G-protem coupled receptor AA098901 Hs 301642 42 2809 6885
453922 budding uninhibited by benzimidazoles 1 AF053306 Hs 36708 42 4467 44688279
410552 fibroblast growth factor receptor 1 (fm X66945 Hs 748 42 4744755144
411213 neuropilin 1 AA676939 Hs 69285 42 519 5179
414178 ESTs, Weakly similar to I38022 hypothet AW957372 Hs 46791 42 788 5396
452873 hypothetical protein FLJ 10385 AK001247 Hs 30922 42 436243638192
429687 nucleoporm 153kD A1675749 Hs 211608 42 2605 6737
452960 protein tyrosine phosphatase, receptor AK001335 Hs 31137 42 4373 8201
448888 caspase recruitment domain protein 6 AW196663 Hs 200242 42 4049 7935
416914 brain and reproductive organ expressed AA344481 Hs 80426 42 1045 5595
411704 hypothetical protein FLJ 10074 AI499220 Hs 71573 42 547 5202
415817 protein tyrosine phosphatase, receptor- U88967 Hs 78867 42 950951 5522
452908 neuronal She adaptor homolog AB001451 Hs 30965 42 436943708198
412723 hypothetical protein AF301222 AA648459 Hs 335951 42 634 5271
428259 ESTs AA424793 Hs 255416 42 2415 6597
414774 plasminogen activator, urokinase X02419 Hs 77274 42 869870 5461
425966 cyclin F NM 001761 Hs 1 973 42 2158 21596409
424893 Homo sapiens cDNA FLJ13303 fis, clone 0AW295112 Hs 153648 41 2020 6313
437162 thyroid hormone receptor coactivating p AW005505 Hs 5464 41 3239 7237
425354 complement component 3a receptor 1 U62027 Hs 155935 41 2093 20946365
441965 ESTs AA972712 Hs 269737 41 3544 7516
405516 ENSP00000200457* Thyroid receptor inter 41 4785
413053 ESTs, Moderately similarto KIAA1399 pi ' AW963263 Hs 65377 41 674 5306
424415 enolase 2, (gamma, neuronal) NMJ01975 Hs 1 46580 4 1 1947 1948 6263
450747 ESTs, Highly imilar to 1818357A EWS ge AI064821 Hs 129953 41 4188 8052
419911 BN51 (BHK21) temperature sensitivity cc i L15301 Hs 1276 41 1393 13945861
441834 KIAA0736 gene product AL138034 Hs7979 41 3539 7511
400252 NM_004651* Homo sapiens ubiquitm speci Hs 171501 41 4609
446006 deafness, autoso al dominant 5 NMJ04403 Hs 1 3530 41 380838097738
416389 integrin, beta 5 AA180072 Hs 149846 41 998 5561
415149 cathepsm L X12451 Hs 78056 41 911 9125490
448633 tubulm, gamma 1 AA311426 Hs 21635 41 4021 7913
416224 reticulocalbin 2, EF hand calcium bindi NM_002902 Hs 9088 41 9839845550
413658 A kinase (PRKA) anchor protein 10 AA055369 Hs 372446 41 734 5351
409132 protein kinase, AMP-activated, beta 2 n AJ224538 Hs 50732 41 3093105025
445133 ESTs AW157646 Hs 198689 41 3745 7690
412749 signal sequence receptor, beta (translo AA378417 Hs 74564 41 635 5272
408716 Homo sapiens mRNA for KIAA1769 protein, AI567839 Hs 151714 41 251 4981
443669 ESTs AI140462 Hs 134587 41 3633 7596
424494 phosphatιdylιnosιtol-4-phosphate 5-kιna U78575 Hs 149255 41 1961 19626273
440524 ESTs R71264 Hs 16798 41 3474 7452
449030 Homo sapiens mRNA for FU00016 prats !in, AI365582 Hs 57100 41 4059 7943
425367 protein tyrosine phosphatase, receptor BE271188 Hs 155975 41 2095 6366
424954 tumor protein p53 (ϋ-Fraumeni syndrome NM-.000546 Hs 1 846 4 1 2031 20326322
448610 nel (chicken) like 1 NM J06157 Hs 21602 41 401940207912
440129 ESTs, Weakly similar to S71886 Ste20-lι AA865818 Hs 369523 4 1 3456 7436
414998 oxidised low density lipoprotein (lecti NM 002543 Hs 7729 40 8988995480
406137 NMJ00179* Homo sapiens mutS (E coli) 40 4802
439246 membrane associated tyrosine- and threo AI498072 Hs 351474 40 3386 7369
430713 eukaryotic translation elongation facto AA351647 Hs 2642 40 2726 6824
434158 ESTs T86534 Hs 14372 40 3031 7064
436703 RNA binding motif protein, X chromosome AW880614 Hs 374352 40 3211 7212
436576 ESTs AI458213 Hs 77542 40 3203 7205
416062 Homo sapiens cDNA FU14609 fis, clone N AA724811 Hs 334791 40 967 5535
456115 titin F01082 Hs 172004 40 4515 8320
427315 Homo sapiens mRNA AA179949 Hs 175563 00 2316 6519
412942 mitogen-activated protein kinase-activa AL120344 Hs 75074 40 658 5293
430233 Homo sapiens mRNA AW367902 Hs 236443 00 2664 6781
446272 hematopoietic cell-specific Lyn substra BE268912 Hs 14601 40 3832 7759
429922 H1 histone family, member 0 Z97630 Hs 226117 40 2621 26226750
450746 general transcription factor II, i D82673 Hs 278589 40 4187 8051
408805 vaccinia related kinase 1 H69912 Hs 48269 40 262 4989
448950 CGI-152 protein AF288687 Hs 9275 40 40504051 7936
409208 integrin, alpha X (antigen CD11C (p150) Y00093 Hs 172631 40 326 327 5038
418918 CD2 antigen (p50), sheep red blood cell X07871 Hs 89476 40 1282 1283 5775
422801 nuclear receptor co repressor 2 AF125672 Hs 287994 40 1739 17406114
421846 protein kinase C substrate 80K-H AA017707 Hs 1432 40 1601 6012
427157 thymme-DNA glycosylase U51166 Hs 173824 40 23052306 6511 449444 solute carrier family 16 (monocarboxyli AW818436 Hs 351306 40 4088 7970 415910 chemokine (C X3-C) receptor 1 U20350 Hs 78913 40 9579585527 445826 Homo sapiens mRNA BE313754 Hs 13350 00 3800 7730 424441 H2A histone family, member X X14850 Hs 147097 40 1952 1953 6267 428134 ESTs AA421773 Hs 161008 40 2401 6586 452355 G protein-coupled receptor 34 N54926 Hs 29202 40 4320 8157 416847 enhancer of filamentation l (cas like d L43821 Hs 80261 40 1039 10405590 443163 ESTs AI082610 Hs 132079 40 3605 7572 405203 NM_002086* Homo sapiens growth factor r 40 4772 407844 ESTs AW073716 Hs 8037 40 168 4912 410545 interleukin 11 receptor, alpha U32324 Hs 64310 40 4724735143 408847 ESTs AW290997 Hs 190153 39 268 4993 443068 ESTs AI188710 Hs 374480 39 3597 7565 412182 Splicing factor, arginine/seππe πch, AA205588 Hs 73737 39 577 5226 452256 Homo sapiens cDNA FU10071 fis, clone H AK000933 Hs 28661 39 4306 8146 449335 STAT induced STAT inhibitor 3 AW150717 Hs 345728 39 4081 7963 453018 ESTs, Weakly similar to Trad [H sapiens AA054522 Hs 61581 39 4379 8207 452888 ephπn-B2 AW955454 Hs 30942 39 4366 8195 403668 Target Exon 39 4727 431629 interferon, alpha-inducible protein (cl AU077025 Hs 265827 39 28036881 407102 glycerol-3-phosphate dehydrogenase 1 (s AA007629 Hs 348601 39 1094861 418005 collagen, type XV, alpha 1 A1186220 Hs 83164 39 11765696 415801 Fc fragment of IgG, low affinity lib, r R24219 Hs 278443 39 9485520 451253 claudm lO H48299 Hs 26126 39 42208078 428245 anaphase promoting complex subunit 11 AF151048 Hs 183180 39 241224136595 424439 ligase I, DNA, ATP-dependent AA579635 Hs 1770 39 19506265 423201 growth hormone receptor NMJ00163 Hs 1 25180 39 178217836146 430053 SEC13 (S cerevisiae) like 1 AF052155 Hs 227949 39 26436766 405372 NM_006841 Homo sapiens transporter prot 39 4778 452239 protein tyrosine phosphatase, receptor AW379378 Hs 356289 39 43038143 450377 KIAA1265 protein AB033091 Hs 355925 39 416041618029 406519 C10001858 gιl6679124|reflNP_032759 1| n 39 4808 413186 solute carπerfamily 16 (monocarboxyli AU077141 Hs 75231 39 6855315 432860 ESTs AW974077 Hs 283349 39 29126967 409649 hypothetical protein FLJ20442 AA159216 Hs 55505 39 3735070 458997 ESTs AW937420 Hs 351869 39 45888384 451063 HLA-B associated transcπpt-2 AW163702 Hs 25911 39 42098069 412810 platelet-derived growth factor receptor M21574 Hs 74615 39 6496505285 426156 natπuretic peptide receptor A guaπylat BE244537 Hs 167382 39 21836427 416110 hypothetical protein DKFZp564A176 Z42262 Hs 322844 39 9745541 437056 gb ok33a11 s1 Soares_NSF_F8_9W_OT_PA_P AI147061 39 32347233 414260 KIAA0218 gene product NMJΪ4760 Hs 75863 39 7937945401 429002 junction plakoglobin AW248439 Hs 2340 38 24986661 435553 KIAA0176 protein D79998 Hs 4935 38 313431357149 428479 cell division cycle 2, G1 to S and G2 t Y00272 Hs 334562 38 244724486623 407202 ESTs N58172 Hs 109370 38 1204872 439863 paired immunoglobulm-like receptor bet BE547830 Hs 375208 38 34347417 409264 KIAA0966 protein NM-014937 Hs 52463 38 3353365043 423798 solute carrier family 4, sodium bicarbo AF047033 Hs 132904 38 185018516196 449843 solute carrier family 31 (copper transp R85337 Hs 24030 38 41177995 446055 mucolipin 1 AI815981 Hs 12909 38 38177745 438330 ESTs AW450572 Hs 257316 38 33167307 418827 HT021 BE327311 Hs 47166 38 12755770 419913 ESTs AW270040 Hs 34455 38 13955862 422241 protein tyrosine phosphatase, receptor Y00062 Hs 170121 38 166316646058 423354 calcium channel, voltage-dependent, alp AB011130 Hs 127436 38 179817996157 433556 calcium/calmodulm dependent protein ki W56321 Hs 111460 38 29877026 402260 NM 001436* Homo sapiens fibπllann (FB 38 4676 436648 ESTs R18656 Hs 349845 38 32097210 400292 NAME OMITTED receptor kinase AA250737 Hs 72472 38 54616 411756 discoidm domain receptor family, membe BE294350 Hs 71891 38 5505205 426691 PCTA1RE protein kinase 1 NMJ06201 Hs 1 71834 38 226222636480 408486 sodium channel voltage-gated, type IV, L04236 Hs 46038 38 2282294960 424240 calcium/calmodulin-dependent protein ki AB023185 Hs 143535 38 191919206242 436434 putative 47 kDa protein N50465 Hs 372732 38 31887193 412432 ESTs AA126311 Hs 9879 38 5855234 421487 seπnefthreonine kinase 23 AF027406 Hs 104865 38 154815495975 400205 NMJ06265* Homo sapiens RAD21 (S pombe Hs 81848 38 4598 429482 transformation/transcription domain-ass AF076974 Hs 203952 38 256725686713 415906 Homo sapiens cDNA FLJ22256 fis, clone AI751357 Hs 288741 38 9565526 424232 protein kinase C, nu AB015982 Hs 143460 38 191719186241 417412 interleukin 1 receptor, type I X16896 Hs 82112 38 111611175652 422105 endosulfine alpha AI929700 Hs 111680 38 16456043 424837 N-acetyltransferase, homolog of S cere BE276113 Hs 333034 38 20106305 412970 dual specificity phosphatase 10 AB026436 Hs 177534 38 6616625295 427217 ESTs AA399272 Hs 144341 38 23106514 437275 ESTs, Weakly similar to A47582 B-cell g AW976035 Hs 292396 38 32517248 435466 G protein beta subunit like BE619165 Hs 29203 37 31287144 408972 DKFZP586D0919 protein AL050100 Hs 49378 37 2872885008 400229 NM 121724* Homo sapiens nuclear recepfo Hs 276916 37 4602 450254 neuropeptide G protein coupled receptor NM_004885 Hs 9 9231 37 414741488018 413472 solute carrier family 1 (glial high aff BE242870 Hs 75379 37 7255342 408105 ESTs, Weakly similar to I38022 hypothet AW152207 Hs 270977 37 1904932 453613 ESTs F06838 Hs 374476 37 44308250 435732 leucine rich repeat and death domain co AF229178 Hs 123136 37 314731487159 450998 splicing factor 3b, subunit 4, 49kD BE387614 Hs 25797 37 42058065 409882 heat shock 27kD protein family, member AJ243191 Hs 56874 37 3953965087 424779 CD37 antigen AL046851 Hs 153053 37 1999 6298 426108 programmed cell death 5 AA622037 Hs 166468 37 2173 6420 428727 general transcription factor IIH, polyp AF078847 Hs 78452 37 246624676637 439237 ESTs, Weakly similarto A47582 B-cell g AW408158 Hs 318893 37 3384 7367 413407 inositol polyphosphate phosphatase-like AI356293 Hs 75339 37 713 5333 430066 signal recognition particle 72kD AI929659 Hs 237825 37 2647 6769 428293 solute earner family 1 (neutral ammo BE250944 Hs 183556 37 2424 6605 438707 ammo acid system N transporter 2 L08239 Hs 5326 00 33503351 7335 418043 AXL receptor tyrosine kinase AW377752 Hs 83341 37 1182 5700 424909 cell division cycle 25B S78187 Hs 153752 37 202420256316 418836 ESTs AI655499 Hs 161712 37 1276 5771 425717 retmoic acid receptor, beta X07282 Hs 171495 37 2131 21326390 428283 Homo sapiens mRNA AI439096 Hs 323079 00 2420 6602 410017 Homo sapiens clone 24775 mRNA sequence AW952426 Hs 109438 37 408 5097 407330 gb πn51b05 s1 NCI_CGAP Kιd6 Homo sapien AA582607 Hs 15628937 136 4884 412760 ESTs AW379030 Hs 41324 37 638 5275 446254 Homo sapiens cDNA FLJ12832 fis, clcne N BE179829 Hs 179852 37 3830 7757 437429 Homo sapiens mRNA H79981 Hs 5613 00 3260 7255 416041 hypothetical protein FLJ13287 AA345547 Hs 53263 37 964 5532 429379 KIAA0537 gene product NM_014840 Hs 200598 37 255225536703 442831 ESTs A1798959 Hs 131686 37 3586 7554 453327 tryptophanyl-tRNA synthetase AW500180 Hs 356109 37 4412 8235 445701 lymphocyte adaptor protein AF055581 Hs 13131 37 379237937724 411887 ESTs AW182924 Hs 128790 37 557 5210 420311 Human DNA sequence from clone RP4-530I1 AW445044 Hs 38207 37 1444 5901 449222 ESTs AW293984 Hs 197621 37 4071 7954 422851 hypothetical protein FLJ22415 AA318060 Hs 135121 37 1750 6121 417767 acyloxyacyl hydrolase (neutrophil) BE242241 Hs 82542 37 1155 5678 407235 SAC2 (suppressor of actin mutations 2, D20569 Hs 169407 36 128 4878 452093 Homo sapiens mRNA AA447453 Hs 27860 00 4286 8129 430440 nerve growth factor, beta polypeptide X52599 Hs 2561 36 2697 26986804 421524 GDNF family receptor alpha 1 AA312082 Hs 105445 36 1556 5980 452882 folate transporter/carrier AW972990 Hs 196270 36 4365 8194 429558 nuoleolar autoaπtigeπ (55 D) similar to AI391454 Hs 207251 36 2579 6721 409190 sarcoma amplified sequence AU076536 Hs 50984 36 321 5034 411411 ESTs, Weakly similar to KIAA1330 protei AA345241 Hs 55950 36 537 5194 414176 EDG-2 (endothelial differentiation, ly BE140638 Hs 75794 36 787 5395 442875 Homo sapiens clone TCCCTA00142 mRNA seq BE623003 Hs 23625 36 3587 7555 428820 integrin, alpha M (complement component AA436187 Hs 172631 36 2476 6644 429732 lymphocyte cytosolic protein 2 (SH2 dom U20158 Hs 2488 36 26102611 6742 422573 integrin, alpha V (vitronectin recepto AW297985 Hs 295726 3 6 1704 6088 432268 3'-phosphoadenosme 5'-phosphosulfate s BE311856 Hs 274230 36 2861 6925 408243 interleukin 8 Y00787 Hs 624 36 2072084946 428648 potassium voltage gated channel, subfam AF052728 Hs 188021 36 245924606632 423072 solute carrier family 12 (sodium/potass AI792946 Hs 123116 36 1776 6141 412791 ESTs, Weakly similar to S72481 probable A1131192 Hs 143199 36 641 5278 441054 ESTs AA913591 Hs 126480 36 3496 7472 439490 ESTs, Weakly similar to A46302 PTB-asso AW249197 Hs 10Q043 36 3401 7384 432179 EphB3 X75208 Hs 2913 36 284928506915 447560 phospholipase A2, group IVC (cytosolic, AF06521 Hs 18858 36 393739387845 454146 calcineuπn-binding protein calsarcιn-1 BE086548 Hs 381047 36 4495 8302 429320 ESTs, Weakly similar to I78885 saπne/t AA449838 Hs 119334 36 2545 6697 413900 stress-induced-phosphoprotein 1 (Hsp70/ AW409747 Hs 75612 36 751 5365 438014 Homo sapιens cDNA FLJ11971 fis, clone H N71183 Hs 121806 36 3296 7289 435021 ESTs AA922192 Hs 73962 36 3097 7116 434398 serum-iπducible kinase (SNK) AA121098 Hs 3838 36 3052 7079 448499 p53-regulated DDA3 BE613280 Hs 77550 36 4008 7905 424156 myotubulaπn related protein 4 AF264717 Hs 141727 36 1905 1906 6234 419700 galactokmase 1 AF084935 Hs 92357 36 1373 13745846 457918 hypothetical protein DKFZp762M186 AL359590 Hs 162604 36 456245638360 413132 protein kinase (cAMP-dependent, catalyt NM M6823 Hs 75209 36 6836845314
TABLE 10B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT Number Accession
418059 1164438 1 AA211586 F35799 F29720AW937408AW937387AA211641
437056 428504_3 AW976398 AI147061 AA765223 AA743380 AI803927
TABLE 10C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers "Dunham I et al " refers to the publication entitled
"The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition
405001 6015406 Minus 104646-104819
403088 8954241 Plus 169894-170193,170504-170806
400499 9796071 Minus 148495-148806 404815 5911819 Minus 64494-64691 400991 8096825 Plus 159197159320 402233 7690102 Plus 90281-91477 405516 9454624 Plus 112707-112876,113676-113854 406137 9166422 Minus 30487-31058 405203 7230116 Plus 125295125463 403668 7259739 Plus 39942-40150 405372 2078459 Minus 10148-10272,11205-11349,11436-11560,1178 406519 3962489 Plus 34617-34928 402260 3399665 Minus 113765113910115653-115765,11680811694
TABLE 11A Pkey Unique Eos probeset identifier number ExAccn Exemplar Accession number, Genbank accession number UπigenelD Unigene number Unigene Title Unigene gene title Seq ID No Sequence Identification Number linking the information in Table 11A to the sequences in Table 12
Pkey ExAccn UnigenelD Unigene Title Seq ID No
450375 AA009647 Hs 8850 a disintegnn and metalloproteinase doma Seq ID No 1 & 32
452838 U65011 Hs 30743 preferentially expressed antigen in mela Seq ID No 2 & 33
429359 W00482 Hs 2399 matnx metalloproteinase 14 (membrane in Seq ID No 3 & 34
428182 BE386042 Hs 293317 ESTs, Weakly similar to GGC1_HUMAN G ANT Seq ID No 4 & 35
418478 U38945 Hs1174 cyclin dependent kinase inhibitor 2A (me Seq ID No 5 & 36
418478 U38945 Hs1174 cyclin dependent kinase inhibitor 2A (me Seq ID No 6 & 37
418478 U38945 Hs1174 cyclin dependent kinase inhibitor 2A (me Seq ID No 7 & 38
418478 U38945 Hs1174 cyclin dependent kinase inhibitor 2A (me Seq ID No 8 & 39
418678 NM 001327 Hs 167379 cancer/testis antigen (NY ESO 1) Seq ID No 9 & 40
418678 NM 01327 Hs 167379 cancer/testis antigen (NY-ESO-1) Seq ID No 10 & 41
404977 Insulin like growth factor 2 (somato edi Seq ID No 11 & 42
450701 H39960 Hs 409224 hypothetical protein XP 98151 (leucine Seq ID No 12 & 43
406687 M31126 Hs 396790 matrix metalloproteinase 11 (stromelys Seq ID No 13 S 44
415989 AI267700 Hs4288 ESTs Seq ID No 14
449048 Z45051 Hs 22920 similar to S68401 (cattle) glucose indue Seq ID No 15 & 45
416658 U03272 Hs 79432 fibnllin 2 (congenital contractural ara Seq ID No 16 & 46
411789 AF245505 Hs 72157 Adlicaπ Seq ID No 17 & 47
417866 AW067903 Hs 82772 collagen, type XI, alpha 1 Seq ID No 18 & 48
417153 X57010 Hs 81343 collagen, type II, alpha 1 (primary oste Seq ID No 1S & 49
426300 U15979 Hs 194693 delta like homolog (Drosophila) Seq ID No 20 & 50
445417 AK001058 Hs 12680 a disintegnn like and metalloprotease w Seq ID No 21 & 51
429329 AA456140 Hs 99235 Homo sapiens pannexm 3 (PANX3) Seq ID No 22 & 52
428305 AA446628 Hs2799 cartilage linking protein 1 Seq ID No 23 & 53
422871 AL031228 Hs 121509 collagen, type XI alpha 2 Seq ID No 24 & 54
441636 AA081846 Hs 407951 Homo sapiens mRNA, cDNA DKFZp566E183 (fr Seq ID No 25 & 55
418399 AF131781 Hs 301989 hypothetical protein FLJ12442 Seq ID No 26 & 56
418140 BE613836 Hs 83551 microfibnllar-associated protein 2 Seq ID No 27 & 57
418140 BE613836 Hs 83551 microfibrillar associated protein 2 Seq ID No 28 & 58
420376 AL137471 Hs 97266 protocadhenn 18 Seq ID No 29 & 59
414477 U41635 Hs 76228 amplified in osteosarcoma Seq ID No 30 & 60
457869 AU077186 Hs 108885 Homo sapiens, alpha 1 (VI) collagen Seq ID No 31 & 61
TABLE 11C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (Gl) numbers Dunham I et al " refers to the publication entitled
The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489 495
Strand Indicates DNA strand from which exons were predicted NLposition Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLposition 404977 3738341 Minus 43081 43229
It is understood that the examples described above in no way serve to limit the true scope of this invention to specific embodiments, but rather are presented for illustrative purposes. All publications, sequences of accession numbers, and patent applications cited in this specification are herein incoφorated by reference as if each individual publication or patent application were specifically and individually indicated to be incoφorated by reference.

Claims

WHAT IS CLAIMED IS:
1. A method of detecting soft tissue sarcoma comprising: a. obtaining a first soft tissue sample from an individual and a normal soft tissue sample from the same individual or from a different individual; b. determining the expression of a gene of Tables 1 A-l IC in the first soft tissue sample and the normal soft tissue sample; and c. comparing the expression of said gene in the first soft tissue sample to expression of said gene in the normal soft tissue sample; wherein a higher level of protein expression in the first soft tissue sample indicates the presence of soft tissue sarcoma.
2. The method of Claim 1, wherein said expression is measured using a labeled nucleic acid probe.
3. The method of Claim 1, wherein said first soft tissue sample and said normal soft tissue sample comprises isolated nucleic acids.
4. The method of Claim 3, wherein the isolated nucleic acids are amplified.
5. The method of Claim 3, wherein said isolated nucleic acids are mRNA.
6. The method of Claim 1, wherein said first soft tissue sample and said normal soft tissue sample comprises isolated polypeptides or proteins.
7. The method of Claim 6, wherein said protein expression is evaluated using antibodies.
8. The method of Claim 1, wherein said expression is measured utilizing a biochip.
9. The method of Claim 8, wherein said biochip comprises nucleic acids complementary to the gene of Tables 1 A-l IC.
10. The method of Claim 8, wherein said biochip comprises antibodies capable of binding a polypeptide or protein encoded by the gene of Tables 1 A-l IC.
11. An antibody that specifically binds a polypeptide or protein encoded by a gene of Tables 1A-1 IC.
12. The antibody of Claim 11 , wherein the antibody is a humanized antibody.
13. The antibody of Claim 11 , wherein the antibody is conjugated to an effector moiety.
14. The antibody of Claim 13, wherein the effector moiety is a labeling moiety or a therapeutic moiety.
15. A method for treating an individual with soft tissue sarcoma comprising administering an antibody of Claim 13.
16. A method for determining the prognosis of a human individual with soft tissue sarcoma cancer comprising determining the expression of a gene of Tables 1 A-l IC in a soft tissue sample of said human individual at different disease stages, wherein the expression of the gene at different disease stages is used to determine the prognosis of the human individual.
17. A method for generating an immune response in an individual to inhibit soft tissue sarcoma cancer comprising: a. purifying a polypeptide encoded by a gene of Tables 1 A-l IC; and b. administering said polypeptide of (a) to an individual.
18. A method for generating an immune response in an individual to inhibit soft tissue sarcoma cancer comprising: a. purifying a nucleic acid of Tables 1 A-l IC; and b. administering said nucleic acid of (a) to an individual.
19. A method for generating a marker for detecting soft tissue sarcoma in a pathological assay, comprising: a. purifying a polypeptide encoded by a gene of Tables 1 A-l 1 C; b. generating a binding partner to the polypeptide of (a); and c. labeling the binding partner.
20. The method of Claim 19, wherein the binding partner is an antibody.
21. A method for screening for an agent capable of binding to a polypeptide encoded by a gene of Tables 1 A-l IC comprising: a. purifying a polypeptide encoded by a gene of Tables 1 A-l IC; b. combining said polypeptide with a plurality of labeled agents; c. capturing said labeled agent(s) bound to the polypeptide of (a) d. identifying the captured agent(s) of (d).
22. The method of Claim 21 , wherein said capturing utilizes an antibody to the polypeptide of (a).
23. A method for screening for an agent capable of binding to a nucleic acid of Tables 1A-11C comprising: a. purifying a nucleic acid of Tables 1 A-l IC; b. combining said nucleic acid with a plurality of labeled agents; c. capturing said labeled agent(s) bound to the labeled nucleic acid of (a); d. identifying the captured agent(s) of (c).
24. A method of screening for a compound that modulates the expression of a gene associated with soft tissue sarcoma comprising: a. monitoring the expression level of a gene of Tables 1 A-l IC in a biological system expressing the gene of Tables 1 A-l IC; b. administering a compound to said biological system; c. comparing the expression of the gene of (a) prior to and after administering the compound; wherein a change in expression level prior to and after administering the compound indicates that the compound is capable of modulating the expression of the gene.
25. A method for detecting the presence of antibodies specific to soft tissue sarcoma, the method comprising: a. obtaining a first soft tissue sample from an individual; b. contacting said soft tissue sample with a polypeptide encoded by a nucleotide sequence of Tables 1A-11C: detecting the binding of antibodies from the soft tissue sample to the polypeptide of(b).
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