Comprehensive molecular characterization of gastric adenocarcinoma

Academic Article

Abstract

  • ©2014 Macmillan Publishers Limited. All rights reserved. Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.
  • Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bass AJ; Thorsson V; Shmulevich I; Reynolds SM; Miller M; Bernard B; Hinoue T; Laird PW; Curtis C; Shen H
  • Start Page

  • 202
  • End Page

  • 209
  • Volume

  • 513
  • Issue

  • 7517