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dc.contributor.authorDulak, A. M.
dc.contributor.authorSchumacher, S. E.
dc.contributor.authorvan Lieshout, J.
dc.contributor.authorImamura, Y.
dc.contributor.authorFox, Cameron
dc.contributor.authorShim, B.
dc.contributor.authorRamos, A. H.
dc.contributor.authorSaksena, G.
dc.contributor.authorBaca, Sylvan Charles
dc.contributor.authorBaselga, J.
dc.contributor.authorTabernero, J.
dc.contributor.authorBarretina, J.
dc.contributor.authorEnzinger, Peter C.
dc.contributor.authorCorso, G.
dc.contributor.authorRoviello, F.
dc.contributor.authorLin, Lin
dc.contributor.authorBandla, S.
dc.contributor.authorLuketich, J. D.
dc.contributor.authorPennathur, A.
dc.contributor.authorMeyerson, Matthew Langer
dc.contributor.authorOgino, Shuji
dc.contributor.authorShivdasani, Ramesh Arjun
dc.contributor.authorBeer, Dennis J
dc.contributor.authorGodfrey, T. E.
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorBass, Adam Joel
dc.date.accessioned2017-05-11T16:44:12Z
dc.date.issued2012
dc.identifier.citationDulak, A. M., S. E. Schumacher, J. van Lieshout, Y. Imamura, C. Fox, B. Shim, A. H. Ramos, et al. 2012. Gastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesis. Cancer Research 72, no. 17: 4383–4393. doi:10.1158/0008-5472.can-11-3893.en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32663219
dc.description.abstractA 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 (SCNAs) 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 utility of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared to 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.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for Cancer Research (AACR)en_US
dc.relation.isversionofdoi:10.1158/0008-5472.CAN-11-3893en_US
dash.licenseLAA
dc.subjectesophagusen_US
dc.subjectstomachen_US
dc.subjectcolonen_US
dc.subjectadenocarcinomaen_US
dc.subjectcopy-numberen_US
dc.titleGastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesisen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalCancer Researchen_US
dash.depositing.authorBeroukhim, Rameen
dc.date.available2017-05-11T16:44:12Z
dc.identifier.doi10.1158/0008-5472.CAN-11-3893*
dash.authorsorderedfalse
dash.contributor.affiliatedFox, Cameron
dash.contributor.affiliatedBeer, Dennis
dash.contributor.affiliatedLin, Lin
dash.contributor.affiliatedBaca, Sylvan
dash.contributor.affiliatedEnzinger, Peter
dash.contributor.affiliatedBass, Adam
dash.contributor.affiliatedMeyerson, Matthew
dash.contributor.affiliatedOgino, Shuji
dash.contributor.affiliatedBeroukhim, Rameen
dash.contributor.affiliatedShivdasani, Ramesh
dc.identifier.orcid0000-0002-9133-8108


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