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LiteratureArticle Details
PMID: 25079317
Published · ppublish
English
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Comprehensive molecular characterization of gastric adenocarcinoma.
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.
MeSH Terms
Adenocarcinoma/classification,genetics,virology
Female
Gene Expression Regulation, Neoplastic
Genome, Human/genetics
Herpesvirus 4, Human/genetics,isolation & purification
Humans
Male
Mutation
Proteome
Stomach Neoplasms/classification,genetics,virology
Chemicals
Proteome
Investigators
315 investigators, click to expand
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2014-09-11
Epub
2014-00-23
Pages
202-9
Language
English
Region
England
NLM ID
0410462
PMCID
PMC4170219
Subset
IM
Grants
NCI NIH HHS · P30CA16672 · United States
NCI NIH HHS · U24 CA143882 · United States
NCI NIH HHS · 5U24CA143840 · United States
NHGRI NIH HHS · R01 HG005690 · United States
NCI NIH HHS · 5U24CA143835 · United States
NCI NIH HHS · U24 CA143843 · United States
NCI NIH HHS · U24 CA143883 · United States
NCI NIH HHS · U24 CA143867 · United States
NCI NIH HHS · 5U24CA143882 · United States
NCI NIH HHS · 5U24CA143799 · United States
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · K99 CA166729 · United States
NCI NIH HHS · P01 CA028842 · United States
NCI NIH HHS · 5U24CA143843 · United States
NHGRI NIH HHS · U54 HG003067 · United States
NHGRI NIH HHS · U54HG003273 · United States
NCI NIH HHS · U24 CA143835 · United States
NCI NIH HHS · 5U24CA143867 · United States
NCI NIH HHS · P30 CA006973 · United States
NCI NIH HHS · 5U24CA143866 · United States
NCI NIH HHS · U24 CA143866 · United States
NCI NIH HHS · K08 CA134931 · United States
NHGRI NIH HHS · R01 HG007069 · United States
NHGRI NIH HHS · U54HG003067 · United States
NCI NIH HHS · U24 CA143845 · United States
NCI NIH HHS · U24 CA143799 · United States
NCI NIH HHS · P50 CA098258 · United States
NCI NIH HHS · 5U24CA144025 · United States
NHGRI NIH HHS · U54 HG003273 · United States
NCI NIH HHS · P30 CA008748 · United States
NCI NIH HHS · U24 CA144025 · United States
NCI NIH HHS · 5U24CA143848 · United States
NHGRI NIH HHS · U54HG003079 · United States
NCI NIH HHS · U24 CA180951 · United States
NCI NIH HHS · U24 CA143840 · United States
NCI NIH HHS · R01 CA180006 · United States
NCI NIH HHS · U24 CA143858 · United States
NCI NIH HHS · 5U24CA143858 · United States
NCI NIH HHS · U24 CA143848 · United States
NCI NIH HHS · U24 CA126543 · United States
Intramural NIH HHS · United States
NCI NIH HHS · 5U24CA143845 · United States
NHGRI NIH HHS · U54 HG003079 · United States
NCI NIH HHS · 5U24CA143883 · United States
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