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A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

Author

Listed:
  • Michael J. Schell

    (Moffitt Cancer Center and Research Institute)

  • Mingli Yang

    (Gibbs Cancer Center and Research Institute)

  • Jamie K. Teer

    (Moffitt Cancer Center and Research Institute)

  • Fang Yin Lo

    (Genomic Services, LabCorp Clinical Trials)

  • Anup Madan

    (Genomic Services, LabCorp Clinical Trials)

  • Domenico Coppola

    (Moffitt Cancer Center and Research Institute)

  • Alvaro N. A. Monteiro

    (Moffitt Cancer Center and Research Institute)

  • Michael V. Nebozhyn

    (Genetics and Pharmacogenomics, Merck, Sharp and Dohme)

  • Binglin Yue

    (Moffitt Cancer Center and Research Institute
    Present address: Xcenda, LLC, Palm Harbor, Florida 34685, USA)

  • Andrey Loboda

    (Genetics and Pharmacogenomics, Merck, Sharp and Dohme)

  • Gabriel A. Bien-Willner

    (Molecular Health)

  • Danielle M. Greenawalt

    (Genetics and Pharmacogenomics, Merck, Sharp and Dohme
    Present address: AstraZeneca, iMED Oncology, Waltham, Massachusetts 02451, USA)

  • Timothy J. Yeatman

    (Gibbs Cancer Center and Research Institute)

Abstract

Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC.

Suggested Citation

  • Michael J. Schell & Mingli Yang & Jamie K. Teer & Fang Yin Lo & Anup Madan & Domenico Coppola & Alvaro N. A. Monteiro & Michael V. Nebozhyn & Binglin Yue & Andrey Loboda & Gabriel A. Bien-Willner & Da, 2016. "A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11743
    DOI: 10.1038/ncomms11743
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    Cited by:

    1. Ilya G. Serebriiskii & Valery Pavlov & Rossella Tricarico & Grigorii Andrianov & Emmanuelle Nicolas & Mitchell I. Parker & Justin Newberg & Garrett Frampton & Joshua E. Meyer & Erica A. Golemis, 2022. "Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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