Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014 Sep 11;513(7517):202-9
Date
08/01/2014Pubmed ID
25079317Pubmed Central ID
PMC4170219DOI
10.1038/nature13480Scopus ID
2-s2.0-84907270779 (requires institutional sign-in at Scopus site) 4585 CitationsAbstract
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.
Author List
Cancer Genome Atlas Research NetworkAuthor
Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenocarcinomaFemale
Gene Expression Regulation, Neoplastic
Genome, Human
Herpesvirus 4, Human
Humans
Male
Mutation
Proteome
Stomach Neoplasms