Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Cancer Cell. 33 p1-15, 2 April 2018 10.1016/j.ccell.2018.03.010

We analyzed 921 adenocarcinomas of esophagus, stomach, colon and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIAC). Hypermutated (HM) tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG Island Methylator Phenotype (CIMP), plus tumors with elevated single nucleotide variants (HM-SNV) associated with mutations in POLE. Tumors with chromosomal instability (CIN) were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed Genome Stable (GS) and enriched in DNA hypermethylation and mutations in KRAS, SOX9 and PCBP1.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (9 Files)

Supplemental Data

• Data Files
  • Key molecular and clinical characteristics of 921 GIACs - Table_S1_Tumor_sample_characteristics.xlsx
  • Selected features for unsupervised clustering and non-GIAC case IDs - Table_S2_Selected_features_for_unsupervised_clustering.xlsx
  • Significantly mutated genes in GIACs - Table_S3_GIAC_significantly_mutated_genes.xlsx
  • Significantly amplified or deleted GISTIC peaks in GIACs - Table_S4_GIAC_somatic_copy-number_alterations.xlsx
  • Genes differentially expressed in GIACs compared with non-GIACs - Table_S5_Differentially_expressed_genes.xlsx
  • Alterations in transcription factors involved in GI development - Table_S6_GIAC_developmental_transcription_factors.xlsx
  • Epigenetic silencing calls in each GIAC case and % silencing in each molecular subtype - Table_S7_GIAC_epigenetic_silencing_calls.xlsx
  • Gene-level amplifications and deletions in each GIAC case - Gene_GISTIC_copy-number.tar.gz
  • Somatic mutations in each GIAC case - Gene_mutations.tar.gz

Additional Resources

• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
• PanCanAtlas Additional Files