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dc.contributor.authorPugh, Trevor J.
dc.contributor.authorWeeraratne, Shyamal Dilhan
dc.contributor.authorArcher, Tenley C.
dc.contributor.authorPomeranz Krummel, Daniel A.
dc.contributor.authorAuclair, Daniel
dc.contributor.authorBochicchio, James
dc.contributor.authorCarneiro, Mauricio O.
dc.contributor.authorCarter, Scott L.
dc.contributor.authorCibulskis, Kristian
dc.contributor.authorErlich, Rachel L.
dc.contributor.authorGreulich, Heidi
dc.contributor.authorLawrence, Michael S.
dc.contributor.authorLennon, Niall J.
dc.contributor.authorMcKenna, Aaron
dc.contributor.authorMeldrim, James
dc.contributor.authorRamos, Alex H.
dc.contributor.authorRoss, Michael G.
dc.contributor.authorRuss, Carsten
dc.contributor.authorShefler, Erica
dc.contributor.authorSivachenko, Andrey
dc.contributor.authorSogoloff, Brian
dc.contributor.authorStojanov, Petar
dc.contributor.authorTamayo, Pablo
dc.contributor.authorMesirov, Jill P.
dc.contributor.authorAmani, Vladimir
dc.contributor.authorTeider, Natalia
dc.contributor.authorSengupta, Soma
dc.contributor.authorFrancois, Jessica Pierre
dc.contributor.authorNorthcott, Paul A.
dc.contributor.authorTaylor, Michael D.
dc.contributor.authorYu, Furong
dc.contributor.authorCrabtree, Gerald R.
dc.contributor.authorKautzman, Amanda G.
dc.contributor.authorGabriel, Stacey B.
dc.contributor.authorGetz, Gad
dc.contributor.authorJäger, Natalie
dc.contributor.authorJones, David T. W.
dc.contributor.authorLichter, Peter
dc.contributor.authorPfister, Stefan M.
dc.contributor.authorRoberts, Thomas M.
dc.contributor.authorMeyerson, Matthew
dc.contributor.authorPomeroy, Scott L.
dc.contributor.authorCho, Yoon-Jae
dc.date.accessioned2013-04-26T17:47:56Z
dc.date.issued2012
dc.identifier.citationPugh, Trevor J., Shyamal Dilhan Weeraratne, Tenley C. Archer, Daniel A. Pomeranz Krummel, Daniel Auclair, James Bochicchio, Mauricio O. Carneiro, et al. 2012. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488(7409): 106-110.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10589789
dc.description.abstractMedulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma.en_US
dc.language.isoen_USen_US
dc.relation.isversionofdoi:10.1038/nature11329en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413789/pdf/en_US
dash.licenseLAA
dc.titleMedulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutationsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNatureen_US
dash.depositing.authorMeyerson, Matthew
dc.date.available2013-04-26T17:47:56Z
dc.identifier.doi10.1038/nature11329*
dash.authorsorderedfalse
dash.contributor.affiliatedSogoloff, Brian
dash.contributor.affiliatedFrancois, Jessica Pierre
dash.contributor.affiliatedSengupta, Soma
dash.contributor.affiliatedRoberts, Thomas
dash.contributor.affiliatedArcher, Tenley
dash.contributor.affiliatedGreulich, Heidi
dash.contributor.affiliatedErlich, R
dash.contributor.affiliatedLennon, Niall
dash.contributor.affiliatedPomeroy, Scott
dash.contributor.affiliatedMesirov, Jill
dash.contributor.affiliatedPugh, Trevor J.
dash.contributor.affiliatedLawrence, Michael
dash.contributor.affiliatedMeyerson, Matthew
dc.identifier.orcid0000-0002-9133-8108


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