Cancer genomics articles from across Nature Portfolio

Relapse in T cell acute lymphoblastic leukemia (T-ALL) constitutes a challenge. A subclonal population of bone marrow progenitor-like cells present in all T-ALL genetic or immunophenotypic subtypes is now shown to confer chemoresistance and poor prognosis, and to be targetable with anti-apoptotic agents.

The early molecular events driving cancer initiation remain elusive, hampering prognostic accuracy. A comparative analysis of 3D genomics data from all stages of colon malignant transformation now reveals that altered connectivity of gene promoters with cognate enhancers is both predictive of and rate-limiting in neoplasia.

Subtyping of non-small cell lung cancer can be challenging based on pathology. Here, the authors utilise multi-omics analysis of 229 patients to identify further subtypes, and altered immune composition between subtypes.

Chromothripsis (CT) is a type of genome instability which is prevalent in medulloblastoma with germline TP53 mutations (Li-Fraumeni syndrome, LFS). Here the authors combine single-cell genomic and transcriptomic analyses to reveal the clonal heterogeneity and functional consequences of CT in LFS medulloblastoma.

Cervical cancer remains a significant public health problem in many regions. Here, the authors perform a proteogenomic analysis of cervical cancer in Chinese patients; they reveal proteomic subgroups associated with clinical and biological features, and a potential biomarker of response to radiotherapy.

Wu et al. perform single-cell analyses to explore the switch from low-grade to high-grade isocitrate-dehydrogenase-mutant glioma and show that it is characterized by oligodendrocyte progenitor cell-like cells transitioning to proliferative neural progenitor cell-like cells.

Epigenetic causes of intra-tumoural heterogeneity are crucial in paediatric cancers with low mutation rates, such as hepatoblastoma. Here, the authors characterise transcriptional heterogeneity in hepatoblastoma using histology-guided RNA sequencing and functional studies in patient-derived tumoroids, and find how the embryonic biliary lineage program, Wnt, and paracrine signalling can promote tumour proliferation.

Relapse in T cell acute lymphoblastic leukemia (T-ALL) constitutes a challenge. A subclonal population of bone marrow progenitor-like cells present in all T-ALL genetic or immunophenotypic subtypes is now shown to confer chemoresistance and poor prognosis, and to be targetable with anti-apoptotic agents.

The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.

Engel et al. conducted a genetic screen in which they identified the Fanconi anaemia (FA) pathway as a driver of chromothripsis, complex genomic rearrangements and generation of extrachromosomal DNA.

In this Journal Club, Chae and Chung discuss a study characterizing the differentiation and maturation of both tumour-resident and circulating B cells in patients with melanoma.

The early molecular events driving cancer initiation remain elusive, hampering prognostic accuracy. A comparative analysis of 3D genomics data from all stages of colon malignant transformation now reveals that altered connectivity of gene promoters with cognate enhancers is both predictive of and rate-limiting in neoplasia.

In this Tools of the Trade article, Carly Tyer describes the development of Telo-seq, a method to enrich and sequence all telomeres within a sample, and highlights its use in distinguishing between the two telomere maintenance mechanisms used in cancer cells.