Comprehensive Molecular Characterization of Gastric Adenocarcinoma

Nature. Volume 513: p202-209. 11 September 2014 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: (1) 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); (2) microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; (3) genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and (4) 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.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (49 Files)
  • Controlled-Access Data - Download Manifest (6 Files)

Supplemental Data

These data represent a data freeze from February 2, 2014.

The data are supported by different organizations. All data marked by [Supplementary] were created by the manuscript authors and you should contact the corresponding author for support.

• S2.4 GISTIC peaks [xlsx]
• S3.5 MutSig data on significantly mutated genes [xlsx]
• S3.7 In-frame rearrangement fusion list [xlsx]
• S3.8 Low-pass structural rearrangements [xlsx]
• S4.3 Genes significantly more frequently silenced in EBV tumours [xlsx]
• S4.4 Epigenetic silencing calls based on HM450 data set [txt]
• S4.5 Epigenetic silencing calls based on HM27-HM450 merged data set [txt]
• S5.4a Overlap list of RNA and whole genome sequencing events [xlsx]
• S5.7a Differentially expressed genes of multiple subtype combinations [xlsx]
• S5.9 Top 20 least variable genes by coefficient of variation [xlsx]
• S6.5 Differentially expressed miRs [xlsx]
• S7.4 List of antibodies used for sample profiling by RPPA [pdf]
• S11.1a Master Patient Table [xlsx]

• Participant List, Sample List, BAM File List, and Full Listing of TCGA Archives for Data Freeze
  • Participant List [txt] [Supplementary]
  • Sample list [txt]
  • Data Freeze List [zip]
  • BAM File Freeze List [txt] [Supplementary]
• Clinical
  • STAD.Clinical.tar [tar] - XML files containing biospecimen processing and clinical data
  • Clinical data spreadsheet [xls]
• Microsatellite Instability
  • Public Microsatellite Instability Data [tar]
  • Level 1 Microsatellite Instability Data [tar]
• Mutations
  • Public Mutations [tar] 679 M
  • Protected Mutations
• IlluminaGA RNASeq and IlluminaHiSeqRNASeq VCF files
  • Protected.STAD.IlluminaGA_RNASeq.Level_2.tar 2.2G
  • Protected.STAD.IlluminaHiSeq_RNASeq.Level_2.tar 29.5G
• Reverse Phase Protein Array (RPPA) Expression
  • Level 4 Data Matrix [Supplementary] - TCGA.255.wo9.xlsx
  • Level 3 Data Archives - STAD.RPPA.Level_3.tar
  • Level 2 Data Archives - STAD.RPPA.Level_2.tar
  • Level 1 Data Archives - STAD.RPPA.Level_1.tar 1.1 G
  • mage-tab Data Archives - STAD.RPPA.mage-tab.tar
• RNA Expression from IlluminaGA RNASeq and IlluminaHiseq RNASeq
  • Level 4 Data Matrix [Supplementary] - RPKM_Expression_Matrix.291Samples_GAF3genes.BCGSC.20131127.tsv 60 M
  • Level 3 Data Archives :
    • STAD.IlluminaGA_RNASeq.Level_3.tar 249 M
    • STAD.IlluminaHiSeq_RNASeq.Level_3.tar 1.9 G
  • mage-tab Data Archives
    • STAD.IlluminaGA_RNASeq.mage-tab.tar
    • STAD.IlluminaHiSeq_RNASeq.mage-tab.tar
• SNP and Copy Number variation from Affymetrix SNP6 and IlluminaHiSeq Low Pass Whole Genome sequencing
  • Level 3 Data Archives :
    • STAD.SNP_6.Level_3.tar 13 M
    • STAD.Level_3_Low_Pass_Sequencing.tar
  • Level 2 Data Archives - Protected.SNP_6.Level_2.tar 31.7G
  • Level 1 Data Archives - Protected.SNP_6.Level_1.tar 19.9G
  • mage-tab Data Archives
    • STAD.SNP_6.mage-tab.tar
    • STAD.Level_3_Low_Pass_Sequencing_MAGE_TAB.tar
• miRNA from Illumina HiSeq 2000 and Illumina GA IIx
  • Level 4 Data Matrix v16 miRBase, v19 miR names [Supplementary] - STAD.miRNASeq.Level_4_expression_matrix_RPM.csv 3.6 M
  • Level 3 Data Archive
    • STAD.IlluminaGA_miRNASeq.Level_3.tar 3.2 M
    • STAD.IlluminaHiSeq_miRNASeq.Level_3.tar 13.5 M
  • mage-tab Archive
    • STAD.IlluminaGA_miRNASeq.mage-tab.tar
    • STAD.IlluminaHiSeq_miRNASeq.mage-tab.tar
• Methylation from Illumina Infinium Human Methylation450 and Methylation27
  • Level 4 Data Matrix [Supplementary] - 20131010_STAD_DNA_Methylation_merged.csv.tar.gz
  • Level 3 Data Archives
    • STAD.Methylation27_Level_3.tar 83.5 M
    • STAD.Methylation450_Level_3.tar 2.47 M
  • Level 2 Data Archives
    • STAD.Methylation27_Level_2.tar 57.9 M
    • STAD.Methylation450_Level_2.tar 2.42 G
  • Level 1 Data Archives
    • STAD.Methylation27_Level_1.tar 57.9 M
    • STAD.Methylation450_Level_1.tar 2.42 G
  • mage-tab Archives
    • STAD.Methylation27_mage-tab.tar
    • STAD.Methylation450_mage-tab.tar

Views of the Data

• Tools for Exploring Data and Analyses
  • cBio Portal, Memorial Sloan-Kettering Cancer Center
  • Regulome Explorer, Institute for Systems Biology
  • HotNet Analysis of Molecular Subtypes, Brown University

Additional Resources

• GDC Encyclopedia
• Descriptions of TCGA data are provided in the TCGA Barcode Encyclopedia Page
• Genomic Data Commons Portal