Integrated genomic characterization of oesophageal carcinoma.


Journal Article

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

Full Text

Duke Authors

Cited Authors

  • Cancer Genome Atlas Research Network, ; Analysis Working Group: Asan University, ; BC Cancer Agency, ; Brigham and Women’s Hospital, ; Broad Institute, ; Brown University, ; Case Western Reserve University, ; Dana-Farber Cancer Institute, ; Duke University, ; Greater Poland Cancer Centre, ; Harvard Medical School, ; Institute for Systems Biology, ; KU Leuven, ; Mayo Clinic, ; Memorial Sloan Kettering Cancer Center, ; National Cancer Institute, ; Nationwide Children’s Hospital, ; Stanford University, ; University of Alabama, ; University of Michigan, ; University of North Carolina, ; University of Pittsburgh, ; University of Rochester, ; University of Southern California, ; University of Texas MD Anderson Cancer Center, ; University of Washington, ; Van Andel Research Institute, ; Vanderbilt University, ; Washington University, ; Genome Sequencing Center: Broad Institute, ; Washington University in St. Louis, ; Genome Characterization Centers: BC Cancer Agency, ; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, ; University of Southern California Epigenome Center, ; Genome Data Analysis Centers: Broad Institute, ; Brown University:, ; University of California Santa Cruz, ; Biospecimen Core Resource: International Genomics Consortium, ; Research Institute at Nationwide Children’s Hospital, ; Tissue Source Sites: Analytic Biologic Services, ; Asan Medical Center, ; Asterand Bioscience, ; Barretos Cancer Hospital, ; BioreclamationIVT, ; Botkin Municipal Clinic, ; Chonnam National University Medical School, ; Christiana Care Health System, ; Cureline, ; Emory University, ; Erasmus University, ; Indiana University School of Medicine, ; Institute of Oncology of Moldova, ; International Genomics Consortium, ; Invidumed, ; Israelitisches Krankenhaus Hamburg, ; Keimyung University School of Medicine, ; National Cancer Center Goyang, ; Ontario Tumour Bank, ; Peter MacCallum Cancer Centre, ; Pusan National University Medical School, ; Ribeirão Preto Medical School, ; St. Joseph’s Hospital &Medical Center, ; St. Petersburg Academic University, ; Tayside Tissue Bank, ; University of Dundee, ; University of Kansas Medical Center, ; University of North Carolina at Chapel Hill, ; University of Pittsburgh School of Medicine, ; Disease Working Group: Duke University, ; Yonsei University College of Medicine, ; Data Coordination Center: CSRA Inc., ; Project Team: National Institutes of Health,

Published Date

  • January 12, 2017

Published In

Volume / Issue

  • 541 / 7636

Start / End Page

  • 169 - 175

PubMed ID

  • 28052061

Pubmed Central ID

  • 28052061

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature20805


  • eng

Conference Location

  • England