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Status: Bibliographieeintrag

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Verfasst von:Pugh, Trevor [VerfasserIn]   i
 Jones, David T. W. [VerfasserIn]   i
 Lichter, Peter [VerfasserIn]   i
 Pfister, Stefan [VerfasserIn]   i
Titel:Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations
Verf.angabe:Trevor J. Pugh, Shyamal Dilhan Weeraratne, Tenley C. Archer, Daniel A. Pomeranz Krummel, Daniel Auclair, James Bochicchio, Mauricio O. Carneiro, Scott L. Carter, Kristian Cibulskis, Rachel L. Erlich, Heidi Greulich, Michael S. Lawrence, Niall J. Lennon, Aaron McKenna, James Meldrim, Alex H. Ramos, Michael G. Ross, Carsten Russ, Erica Shefler, Andrey Sivachenko, Brian Sogoloff, Petar Stojanov, Pablo Tamayo, Jill P. Mesirov, Vladimir Amani, Natalia Teider, Soma Sengupta, Jessica Pierre Francois, Paul A. Northcott, Michael D. Taylor, Furong Yu, Gerald R. Crabtree, Amanda G. Kautzman, Stacey B. Gabriel, Gad Getz, Natalie Jäger, David T.W. Jones, Peter Lichter, Stefan M. Pfister, Thomas M. Roberts, Matthew Meyerson, Scott L. Pomeroy & Yoon-Jae Cho
E-Jahr:2012
Jahr:22 July 2012
Umfang:5 S.
Fussnoten:Gesehen am 27.11.2018
Titel Quelle:Enthalten in: Nature <London>
Ort Quelle:London [u.a.] : Nature Publ. Group, 1869
Jahr Quelle:2012
Band/Heft Quelle:488(2012), 7409, Seite 106-110
ISSN Quelle:1476-4687
Abstract:Medulloblastomas are the most common malignant brain tumours in children1. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles2,3,4,5. Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, 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 newly 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. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, β-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 β-catenin signalling in medulloblastoma.
DOI:doi:10.1038/nature11329
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

: Volltext ; Verlag: http://dx.doi.org/10.1038/nature11329
 : Volltext: https://www.nature.com/articles/nature11329
 : : https://doi.org/10.1038/nature11329
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1584493593
Verknüpfungen:→ Zeitung

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