Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis.

Abstract

A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions.

• Authors: Austin M Dulak, Steven E Schumacher, Jasper van Lieshout, Yu Imamura, Cameron Fox, Byoungyong Shim, Alex H Ramos, Gordon Saksena, Sylvan C Baca, Jose Baselga, Josep Tabernero, Jordi Barretina, Peter C Enzinger, Giovanni Corso, Franco Roviello, Lin Lin, Santhoshi Bandla, James D Luketich, Arjun Pennathur, Matthew Meyerson, Shuji Ogino, Ramesh A Shivdasani, David G Beer, Tony E Godfrey, Rameen Beroukhim, Adam J Bass
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 17 Pg. 4383-93 (Sep 01 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22751462 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Core Binding Factor Alpha 2 Subunit

Topics

• Adenocarcinoma (genetics)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• Chromosome Aberrations
• Cluster Analysis
• Colonic Neoplasms (genetics)
• Core Binding Factor Alpha 2 Subunit (genetics)
• DNA Copy Number Variations
• Esophageal Neoplasms (genetics)
• Gastrointestinal Neoplasms (genetics)
• Gene Deletion
• Genomic Instability
• Genomics
• Humans
• Stomach Neoplasms (genetics)