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dc.contributor.authorShankar, Ganesh Mani
dc.contributor.authorTaylor-Weiner, Amaro
dc.contributor.authorLelic, Nina
dc.contributor.authorJones, Robert T
dc.contributor.authorKim, James C
dc.contributor.authorFrancis, Joshua M
dc.contributor.authorAbedalthagafi, Malak S
dc.contributor.authorBorges, Lawrence Francis
dc.contributor.authorCoumans, Jean-Valery C E
dc.contributor.authorCurry, William Thomas
dc.contributor.authorNahed, Brian Vala
dc.contributor.authorShin, John H
dc.contributor.authorPaek, Sun Ha
dc.contributor.authorPark, Sung-Hye
dc.contributor.authorStewart, Chip
dc.contributor.authorLawrence, Michael S
dc.contributor.authorCibulskis, Kristian
dc.contributor.authorThorner, Aaron R
dc.contributor.authorVan Hummelen, Paul
dc.contributor.authorStemmer-Rachamimov, Anat
dc.contributor.authorBatchelor, Tracy Todd
dc.contributor.authorCarter, Scott Lambert
dc.contributor.authorHoang, Mai P
dc.contributor.authorSantagata, Sandro
dc.contributor.authorLouis, David N.
dc.contributor.authorBarker, Frederick George
dc.contributor.authorMeyerson, Matthew Langer
dc.contributor.authorGetz, Gad A
dc.contributor.authorBrastianos, Priscilla Kalliope
dc.contributor.authorCahill, Daniel P.
dc.date.accessioned2018-05-14T15:23:38Z
dc.date.issued2014
dc.identifier.citationShankar, Ganesh M, Amaro Taylor-Weiner, Nina Lelic, Robert T Jones, James C Kim, Joshua M Francis, Malak Abedalthagafi, et al. 2014. Sporadic Hemangioblastomas Are Characterized by Cryptic VHL Inactivation. Acta Neuropathol Commun 2, no. 1. doi:10.1186/s40478-014-0167-x.en_US
dc.identifier.issn2051-5960en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:36880596
dc.description.abstractHemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isversionofdoi:10.1186/s40478-014-0167-xen_US
dash.licenseLAA
dc.subjectcentral nervous systemen_US
dc.subjecthemangioblastomaen_US
dc.subjectdeep sequencingen_US
dc.subjectsomatic gene alterationsen_US
dc.subjectVon Hippel-Lindau geneen_US
dc.subjecthypoxia-inducible signalingen_US
dc.titleSporadic hemangioblastomas are characterized by cryptic VHL inactivationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalActa Neuropathologica Communicationsen_US
dash.depositing.authorNahed, Brian Vala
dc.date.available2018-05-14T15:23:38Z
dc.identifier.doi10.1186/s40478-014-0167-x*
dash.authorsorderedfalse
dash.contributor.affiliatedCoumans, Jean-Valery
dash.contributor.affiliatedShin, John
dash.contributor.affiliatedBorges, Lawrence
dash.contributor.affiliatedTaylor-Weiner, Amaro
dash.contributor.affiliatedHoang, Mai
dash.contributor.affiliatedAbedalthagafi, Malak
dash.contributor.affiliatedBrastianos, Priscilla
dash.contributor.affiliatedShankar, Ganesh
dash.contributor.affiliatedBarker, Frederick
dash.contributor.affiliatedLouis, David
dash.contributor.affiliatedStemmer-Rachamimov, Anat
dash.contributor.affiliatedNahed, Brian
dash.contributor.affiliatedCurry, William
dash.contributor.affiliatedCahill, Daniel
dash.contributor.affiliatedCarter, Scott
dash.contributor.affiliatedSantagata, Sandro
dash.contributor.affiliatedBatchelor, Tracy
dash.contributor.affiliatedGetz, Gad
dash.contributor.affiliatedMeyerson, Matthew
dc.identifier.orcid0000-0001-7803-9683
dc.identifier.orcid0000-0002-9133-8108


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