The genetic landscape of the childhood cancer medulloblastoma

D. Williams Parsons, Meng Li, Xiaosong Zhang, Siân Jones, Rebecca J. Leary, Jimmy Cheng Ho Lin, Simina M. Boca, Hannah Carter, Josue Samayoa, Chetan Bettegowda, Gary L. Gallia, George I. Jallo, Zev A. Binder, Yuri Nikolsky, James Hartigan, Doug R. Smith, Daniela S. Gerhard, Daniel W. Fults, Scott VandenBerg, Mitchel S. BergerSuely Kazue Nagahashi Marie, Sueli Mieko Oba Shinjo, Carlos Clara, Peter C. Phillips, Jane E. Minturn, Jaclyn A. Biegel, Alexander R. Judkins, Adam C. Resnick, Phillip B. Storm, Tom Curran, Yiping He, B. Ahmed Rasheed, Henry S. Friedman, Stephen T. Keir, Roger McLendon, Paul A. Northcott, Michael D. Taylor, Peter C. Burger, Gregory J. Riggins, Rachel Karchin, Giovanni Parmigiani, Darell D. Bigner, Hai Yan, Nick Papadopoulos, Bert Vogelstein, Kenneth W. Kinzler, Victor E. Velculescu

Research output: Contribution to journalArticlepeer-review

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

Original languageEnglish (US)
Pages (from-to)435-439
Number of pages5
JournalScience
Volume331
Issue number6016
DOIs
StatePublished - Jan 28 2011

ASJC Scopus subject areas

  • General

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