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

Authors: Northcott, PA  Nakahara, Y  Wu, X  Feuk, L  Ellison, DW  Croul, S  Mack, S  Kongkham, PN  Peacock, J  Dubuc, A  Ra, YS  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 
Citation: Northcott PA, etal., Nat Genet. 2009 Apr;41(4):465-72. doi: 10.1038/ng.336. Epub 2009 Mar 8.
Pubmed: (View Article at PubMed) PMID:19270706
DOI: Full-text: DOI:10.1038/ng.336

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.


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CRRD Object Information
CRRD ID: 9587481
Created: 2014-10-15
Species: All species
Last Modified: 2014-10-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.