Publication

Comprehensive molecular characterization of gastric adenocarcinoma.

Nature. 2014 Jul 23. doi: 10.1038/nature13480. [Epub ahead of print]

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

The Cancer Genome Atlas Research Network; Analysis Working Group: Dana-Farber Cancer Institute; Institute for Systems Biology; University of Southern California; Memorial Sloan Kettering Cancer Center; BC Cancer Agency; The Eli &Edythe L. Broad Institute; MD Anderson Cancer Center; Harvard Medical School; University of North Carolina; Vanderbilt University; Asan Medical Center; University of Melbourne; National Cancer Institute; Case Western Reserve University; University of California at Santa Cruz; Duke University; University of Michigan; University of Pittsburgh; Brown University; Brigham and Women’s Hospital; National Cancer Center; Nationwide Children’s Hospital; Washington University; Greater Poland Cancer Centre; KU Leuven; Genome Sequencing Center: The Eli &Edythe L. Broad Institute; Washington University in St. Louis; Genome Characterization Centers: BC Cancer Agency; The Eli &Edythe L. Broad Institute; Harvard Medical School/Brigham &Women’s Hospital/MD Anderson Cancer Center; MD Anderson Cancer Center; University of Southern California Epigenome Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; Genome Data Analysis Centers: The Eli &Edythe L. Broad Institute; Memorial Sloan-Kettering Cancer Cente; Institute for Systems Biology; University of California, Santa Cruz; MD Anderson Cancer Center; Brown University; University of California San Francisco; Biospecimen Core Resource: The Research Institute at Nationwide Children’s Hospital; International Genomics Consortium; Tissue Source Sites: Buck Institute for Research on Aging; Chonnam National University Medical School; City Clinical Oncology Dispensary; Cureline; UNC Lineberger Comprehensive Cancer Center; Greater Poland Cancer Centre; Helen F. Graham Cancer Center &Research Institute; Keimyung University School of Medicine; International Genomics Consortium; Ontario Tumour Bank; Pusan National University Hospital; University of Pittsburgh School of Medicine; Disease Working Group: Memorial Sloan-Kettering Cancer Center; Duke University; Asan Medical Center; Yonsei University College of Medicine; MD Anderson Cancer Center; National Cancer Institute; Data Coordination Center: SRA International; Project Team: National Cancer Institute; SAIC-Frederick; Analysis Working Group Dana-Farber Cancer Institute; Institute for Systems Biology; University of Southern California; Memorial Sloan Kettering Cancer Center; BC Cancer Agency; The Eli Edythe L Broad Institute; MD Anderson Cancer Center; Harvard Medical School; University of North Carolina; Vanderbilt University; Asan Medical Center; University of Melbourne; National Cancer Institute; Case Western Reserve University; University of California at Santa Cruz; Duke University; University of Michigan; University of Pittsburgh; Brown University; Brigham and Women's Hospital; National Cancer Center; Nationwide Children's Hospital; Washington University; Greater Poland Cancer Centre; KU Leuven; Genome Sequencing Center The Eli Edythe L Broad Institute; Washington University in St Louis; Genome Characterization Centers BC Cancer Agency; The Eli Edythe L Broad Institute; Harvard Medical School/Brigham Women's Hospital/MD Anderson Cancer Center; MD Anderson Cancer Center; University of Southern California Epigenome Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; Genome Data Analysis Centers The Eli Edythe L Broad Institute; Memorial Sloan-Kettering Cancer Cente; Institute for Systems Biology; University of California Santa Cruz; MD Anderson Cancer Center; Brown University; University of California San Francisco; Biospecimen Core Resource The Research Institute at Nationwide Children's Hospital; International Genomics Consortium; Tissue Source Sites Buck Institute for Research on Aging; Chonnam National University Medical School; City Clinical Oncology Dispensary; Cureline; UNC Lineberger Comprehensive Cancer Center; Greater Poland Cancer Centre; Helen F Graham Cancer Center Research Institute; Keimyung University School of Medicine; International Genomics Consortium; Ontario Tumour Bank; Pusan National University Hospital; University of Pittsburgh School of Medicine; Disease Working Group Memorial Sloan-Kettering Cancer Center; Duke University; Asan Medical Center; Yonsei University College of Medicine; MD Anderson Cancer Center; National Cancer Institute; Data Coordination Center SRA International; Project Team National Cancer Institute; SAIC-Frederick; SAIC-Frederick.

Institute Authors

Li Ding, Ph.D., Mike McLellan