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dc.contributor.authorLe, Long Phi
dc.contributor.authorNielsen, Gunnlaugur Petur
dc.contributor.authorRosenberg, Andrew Eric
dc.contributor.authorThomas, Dafydd
dc.contributor.authorBatten, Julie M.
dc.contributor.authorDeshpande, Vikram
dc.contributor.authorSchwab, Joseph H
dc.contributor.authorDuan, Zhenfeng
dc.contributor.authorXavier, Ramnik
dc.contributor.authorHornicek, Francis John
dc.contributor.authorIafrate, Anthony John
dc.date.accessioned2011-12-01T18:45:10Z
dc.date.issued2011
dc.identifier.citationLe, Long Phi, G. Petur Nielsen, Andrew Eric Rosenberg, Dafydd Thomas, Julie M. Batten, Vikram Deshpande, Joseph Schwab, Zhenfeng Duan, Ramnik J. Xavier, Francis J. Hornicek, and A. John Iafrate. 2011. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS ONE 6(5): e18846.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5358871
dc.description.abstractThe molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0018846en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094331/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectcomputational biologyen_US
dc.subjectmicroarraysen_US
dc.subjectgenomicsen_US
dc.subjectchromosome biologyen_US
dc.subjectmedicineen_US
dc.subjectclinical geneticsen_US
dc.subjectchromosomal disordersen_US
dc.subjectdiagnostic medicineen_US
dc.subjectpathologyen_US
dc.subjectgeneral pathologyen_US
dc.subjectmolecular pathologyen_US
dc.subjectoncologyen_US
dc.subjectcancer risk factorsen_US
dc.subjectgenetic causes of canceren_US
dc.subjectcancers and neoplasmsen_US
dc.subjectbone and soft tissue sarcomasen_US
dc.subjectbasic cancer researchen_US
dc.titleRecurrent Chromosomal Copy Number Alterations in Sporadic Chordomasen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorRosenberg, Andrew Eric
dc.date.available2011-12-01T18:45:10Z
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Orthopedic Surgery-Mass General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0018846*
dash.contributor.affiliatedSchwab, Joseph
dash.contributor.affiliatedRosenberg, Andrew Eric
dash.contributor.affiliatedNielsen, Gunnlaugur
dash.contributor.affiliatedIafrate, Anthony
dash.contributor.affiliatedLe, Long Phi
dash.contributor.affiliatedHornicek, Francis
dash.contributor.affiliatedDeshpande, Vikram
dash.contributor.affiliatedXavier, Ramnik


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