title: 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: Departments of Medical Oncology, Cancer Biology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors: Austin M
authors: AM
authors: Dulak
authors: Steven E
authors: SE
authors: Schumacher
authors: Jasper
authors: J
authors: van Lieshout
authors: Yu
authors: Y
authors: Imamura
authors: Cameron
authors: C
authors: Fox
authors: Byoungyong
authors: B
authors: Shim
authors: Alex H
authors: AH
authors: Ramos
authors: Gordon
authors: G
authors: Saksena
authors: Sylvan C
authors: SC
authors: Baca
authors: Jose
authors: J
authors: Baselga
authors: Josep
authors: J
authors: Tabernero
authors: Jordi
authors: J
authors: Barretina
authors: Peter C
authors: PC
authors: Enzinger
authors: Giovanni
authors: G
authors: Corso
authors: Franco
authors: F
authors: Roviello
authors: Lin
authors: L
authors: Lin
authors: Santhoshi
authors: S
authors: Bandla
authors: James D
authors: JD
authors: Luketich
authors: Arjun
authors: A
authors: Pennathur
authors: Matthew
authors: M
authors: Meyerson
authors: Shuji
authors: S
authors: Ogino
authors: Ramesh A
authors: RA
authors: Shivdasani
authors: David G
authors: DG
authors: Beer
authors: Tony E
authors: TE
authors: Godfrey
authors: Rameen
authors: R
authors: Beroukhim
authors: Adam J
authors: AJ
authors: Bass
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D042822:Genomic Instability; D023281:Genomics; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit