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Nat Commun. 2016 Jun 15;7:11743. doi: 10.1038/ncomms11743.

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

Author information

1
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
2
Gibbs Cancer Center and Research Institute, 380 Serpentine Drive, Spartanburg, South Carolina 29303, USA.
3
Genomic Services, LabCorp Clinical Trials, 401 Terry Avenue North, Suite 200, Seattle, Washington 98109, USA.
4
Department of Anatomic Pathology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
5
Department of Epidemiology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
6
Genetics and Pharmacogenomics, Merck, Sharp and Dohme, PO Box 4, 770 Sumneytown Pike, Building 53, West Point, Pennsylvania 19486, USA.
7
Molecular Health, 2700 Technology Forest Boulevard, The Woodlands, Texas 77381, USA.

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.

PMID:
27302369
PMCID:
PMC4912618
DOI:
10.1038/ncomms11743
[Indexed for MEDLINE]
Free PMC Article

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