Comprehensive molecular characterization of gastric adenocarcinoma.

Cancer Genome Atlas Research Network
Nature. 2014 513 (7517): 202-9

PMID: 25079317 · PMCID: PMC4170219 · DOI:10.1038/nature13480

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.

MeSH Terms (10)

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

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