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

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, Danielle M. Greenawalt and Timothy J. Yeatman ()
Additional contact information
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
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
Timothy J. Yeatman: Gibbs Cancer Center and Research Institute

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11743

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