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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Adenomatous Polyposis Coli Protein / metabolism
  • Cell Nucleus / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Genes, Neoplasm
  • Humans
  • Kaplan-Meier Estimate
  • Microsatellite Instability
  • Mutation / genetics*
  • Mutation Rate
  • Neoplasm Metastasis
  • Prognosis
  • Proportional Hazards Models
  • Staining and Labeling
  • Statistics, Nonparametric
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics
  • beta Catenin / metabolism

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Wnt Proteins
  • beta Catenin