Comprehensive molecular characterization of gastric adenocarcinoma

Nature. 2014 Sep 11;513(7517):202-9. doi: 10.1038/nature13480. Epub 2014 Jul 23.

Abstract

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.

Publication types

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

MeSH terms

  • Adenocarcinoma / classification*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / virology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Male
  • Mutation
  • Proteome
  • Stomach Neoplasms / classification*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / virology

Substances

  • Proteome

Grants and funding