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Uncovering Clinically Relevant Gene Fusions with Integrated Genomic and Transcriptomic Profiling of Metastatic Cancers.

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Author information

Affiliations

  • 1. Department of Medical Oncology, BC Cancer, Vancouver, Canada.
      Authors
    • Tsang ES 1
    • Sun S 1
    • Lim HJ 1
    • Renouf DJ 1, 3
    • Laskin J 1
    • Loree JM 1
    (6 authors)
  • 2. Canada's Michael Smith Genome Sciences Centre at BC Cancer, Vancouver, Canada.
      Authors
    • Grisdale CJ 2
    • Pleasance E 2
    • Mungall K 2
    • Reisle C 2
    • Choo C 2
    • Carreira M 2
    • Bowlby R 2
    • MacMillan D 2
    • Williamson LM 2
    • Chuah E 2
    • Moore RA 2
    • Mungall AJ 2
    • Zhao Y 2
    • Tessier-Cloutier B 2
    • Marra MA 2
    • Jones SJM 2
    (16 authors)
  • 3. Pancreas Centre BC, Vancouver, Canada.
      Authors
    • Topham JT 3
    • Karasinska JM 3
    • Schaeffer DF 3, 4
    • Renouf DJ 1, 3
    (4 authors)
  • 4. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
      Authors
    • Ng T 4
    • Schaeffer DF 3, 4
    • Yip S 4
    (3 authors)

ORCIDs linked to this article

Show all (9)

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 04 Nov 2020, 27(2):522-531
https://doi.org/10.1158/1078-0432.ccr-20-1900 PMID: 33148671 

Abstract 

Purpose

Gene fusions are important oncogenic drivers and many are actionable. Whole-genome and transcriptome (WGS and RNA-seq, respectively) sequencing can discover novel clinically relevant fusions.

Experimental design

Using WGS and RNA-seq, we reviewed the prevalence of fusions in a cohort of 570 patients with cancer, and compared prevalence to that predicted with commercially available panels. Fusions were annotated using a consensus variant calling pipeline (MAVIS) and required that a contig of the breakpoint could be constructed and supported from ≥2 structural variant detection approaches.

Results

In 570 patients with advanced cancer, MAVIS identified 81 recurrent fusions by WGS and 111 by RNA-seq, of which 18 fusions by WGS and 19 by RNA-seq were noted in at least 3 separate patients. The most common fusions were EML4-ALK in thoracic malignancies (9/69, 13%), and CMTM8-CMTM7 in colorectal cancer (4/73, 5.5%). Combined genomic and transcriptomic analysis identified novel fusion partners for clinically relevant genes, such as NTRK2 (novel partners: SHC3, DAPK1), and NTRK3 (novel partners: POLG, PIBF1).

Conclusions

Utilizing WGS/RNA-seq facilitates identification of novel fusions in clinically relevant genes, and detected a greater proportion than commercially available panels are expected to find. A significant benefit of WGS and RNA-seq is the innate ability to retrospectively identify variants that becomes clinically relevant over time, without the need for additional testing, which is not possible with panel-based approaches.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/1078-0432.ccr-20-1900

Read article for free, from open access legal sources, via Unpaywall: https://aacrjournals.org/clincancerres/article-pdf/27/2/522/2066227/522.pdfUnpaywall

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Funding 

Funders who supported this work.

CIHR (1)