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dc.contributor.authorSheffer, Michal
dc.contributor.authorBacolod, Manny D.
dc.contributor.authorZuk, Or
dc.contributor.authorGiardina, Sarah F.
dc.contributor.authorPincas, Hanna
dc.contributor.authorBarany, Francis
dc.contributor.authorPaty, Philip B.
dc.contributor.authorGerald, William L.
dc.contributor.authorNotterman, Daniel A.
dc.contributor.authorDomany, Eytan
dc.date.accessioned2009-12-28T15:03:21Z
dc.date.available2009-12-28T15:03:21Z
dc.date.issued2009-04
dc.date.submitted2008-10
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1721.1/50248
dc.description.abstractDuring disease progression the cells that comprise solid malignancies undergo significant changes in gene copy number and chromosome structure. Colorectal cancer provides an excellent model to study this process. To indentify and characterize chromosomal abnormalities in colorectal cancer, we performed a statistical analysis of 299 expression and 130 SNP arrays profiled at different stages of the disease, including normal tissue, adenoma, stages 1–4 adenocarcinoma, and metastasis. We identified broad (> 1/2 chromosomal arm) and focal (< 1/2 chromosomal arm) events. Broad amplifications were noted on chromosomes 7, 8q, 13q, 20, and X and broad deletions on chromosomes 4, 8p, 14q, 15q, 17p, 18, 20p, and 22q. Focal events (gains or losses) were identified in regions containing known cancer pathway genes, such as VEGFA, MYC, MET, FGF6, FGF23, LYN, MMP9, MYBL2, AURKA, UBE2C, and PTEN. Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including CCDC68, CSMD1, POLR1D, and PMEPA1. From the expression data, we identified genes whose expression levels reflected their copy number changes and used this relationship to impute copy number changes to samples without accompanying SNP data. This analysis provided the statistical power to show that deletions of 8p, 4p, and 15q are associated with survival and disease progression, and that samples with simultaneous deletions in 18q, 8p, 4p, and 15q have a particularly poor prognosis. Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis.en
dc.description.sponsorshipGilbert Family Foundationen
dc.description.sponsorshipHilton-Ludwig Cancer Metastasis Initiativeen
dc.description.sponsorshipRidgefield Foundationen
dc.description.sponsorshipNational Cancer Instituteen
dc.language.isoen_US
dc.publisherNational Academy of Sciencesen
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0902232106en
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en
dc.sourcePNASen
dc.titleAssociation of survival and disease progression with chromosomal instability: A genomic exploration of colorectal canceren
dc.typeArticleen
dc.identifier.citationSheffer, Michal et al. “Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer.” Proceedings of the National Academy of Sciences 106.17 (2009): 7131-7136.en
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.contributor.approverZuk, Or
dc.contributor.mitauthorZuk, Or
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen
dc.eprint.versionFinal published versionen
dc.identifier.pmid19359472
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
eprint.grantNumber263 MQ 610681en
eprint.grantNumberP01-CA65930en
dspace.orderedauthorsSheffer, M.; Bacolod, M. D.; Zuk, O.; Giardina, S. F.; Pincas, H.; Barany, F.; Paty, P. B.; Gerald, W. L.; Notterman, D. A.; Domany, E.en
mit.licensePUBLISHER_POLICYen
mit.metadata.statusComplete


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