Comprehensive molecular characterization of gastric adenocarcinoma. Academic Article uri icon

Overview

MeSH

  • Female
  • Gene Expression Regulation, Neoplastic
  • Herpesvirus 4, Human
  • Humans
  • Male
  • Mutation
  • Proteome

MeSH Major

  • Adenocarcinoma
  • Genome, Human
  • Stomach Neoplasms

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.

authors

publication date

  • September 11, 2014

has subject area

  • Adenocarcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Herpesvirus 4, Human
  • Humans
  • Male
  • Mutation
  • Proteome
  • Stomach Neoplasms

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4170219

Digital Object Identifier (DOI)

  • 10.1038/nature13480

PubMed ID

  • 25079317

Additional Document Info

start page

  • 202

end page

  • 209

volume

  • 513

number

  • 7517