Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.

Published

Journal Article

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Full Text

Duke Authors

Cited Authors

  • Northcott, PA; Nakahara, Y; Wu, X; Feuk, L; Ellison, DW; Croul, S; Mack, S; Kongkham, PN; Peacock, J; Dubuc, A; Ra, Y-S; Zilberberg, K; McLeod, J; Scherer, SW; Sunil Rao, J; Eberhart, CG; Grajkowska, W; Gillespie, Y; Lach, B; Grundy, R; Pollack, IF; Hamilton, RL; Van Meter, T; Carlotti, CG; Boop, F; Bigner, D; Gilbertson, RJ; Rutka, JT; Taylor, MD

Published Date

  • April 2009

Published In

Volume / Issue

  • 41 / 4

Start / End Page

  • 465 - 472

PubMed ID

  • 19270706

Pubmed Central ID

  • 19270706

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.336

Language

  • eng