TCGA Stomach Adenocarcinoma (STAD)

Overview

Multi-platform molecular characterization of 295 primary, treatment-naive gastric adenocarcinomas performed by The Cancer Genome Atlas (TCGA) Research Network. The study defines four molecular subtypes — EBV-positive, microsatellite instable (MSI), genomically stable (GS), and chromosomally instable (CIN) — providing a taxonomy for biomarker-stratified clinical trials in gastric cancer.

Composition

  • Cancer type: gastric/stomach adenocarcinoma (STAD)
  • 295 treatment-naive patients (surgery); 77% profiled on all six molecular platforms
  • Non-malignant gastric tissue controls: methylation n=27, expression n=29
  • 107 tumor/germline pairs with low-pass whole-genome sequencing (<6×)
  • Subtype distribution: EBV 9%, MSI 22%, GS 20%, CIN 50%

Assays / panels (linked)

Papers using this cohort

  • PMID:25079317 — TCGA Research Network 2014, comprehensive molecular characterization of gastric adenocarcinoma

Notable findings derived from this cohort

  • Four-subtype classification: EBV-positive (9%), MSI (22%), GS (20%), CIN (50%); each subtype defined by a distinct molecular signature and therapeutic vulnerability profile PMID:25079317
  • EBV-positive tumors: extreme CIMP, 9p24.1 amplification of JAK2/CD274/PDCD1LG2 (15%), PIK3CA mutations in 80%, supporting PD-L1/L2 immune-checkpoint blockade and JAK2 inhibition PMID:25079317
  • MSI tumors: MLH1 promoter hypermethylation drives MSI; 37 significantly mutated genes after indel inclusion; BRAF V600E absent (unlike MSI colorectal cancer) PMID:25079317
  • GS tumors: RHOA mutations in 15% and CLDN18-ARHGAP26/ARHGAP6 fusions in 15% are mutually exclusive and together affect 30% of GS cases; enriched for diffuse Lauren histology (73%) PMID:25079317
  • CIN tumors: TP53 mutation in 71%; recurrent focal amplifications of ERBB2, KRAS, MYC, EGFR, CCNE1, CDK6, VEGFA PMID:25079317
  • MET exon 2 skipping in 30% and exon 18/19 skipping in 17% across the full cohort PMID:25079317
  • Used as validation cohort for BRCA2 mutation-survival analysis in gastric adenocarcinoma; 289 cases with 28 BRCA2-mutant tumors contributed to pooled log-rank P=0.03 survival association, and ERBB4 kinase-domain mutations (p.V744L, p.774N/G) and NRG1ERBB4 mutual exclusivity confirmed in this cohort PMID:25583476
  • Provided 359 gastric adenocarcinoma samples as historical comparator for the TCGA oesophageal-stomach combined analysis; 77 additional STADs not in the original stad_tcga_pub were incorporated into stes_tcga_pub PMID:28052061

Sources

  • cBioPortal studyId: stad_tcga_pub
  • TCGA Data Portal

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