@article{852eb96bb1634652bd1a80fef1a57164,
title = "Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma",
abstract = "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.",
author = "Northcott, {Paul A.} and Yukiko Nakahara and Xiaochong Wu and Lars Feuk and Ellison, {David W.} and Sid Croul and Stephen Mack and Kongkham, {Paul N.} and John Peacock and Adrian Dubuc and Ra, {Young Shin} and Karen Zilberberg and Jessica Mcleod and Scherer, {Stephen W.} and {Sunil Rao}, J. and Eberhart, {Charles G.} and Wiesia Grajkowska and Yancey Gillespie and Boleslaw Lach and Richard Grundy and Pollack, {Ian F.} and Hamilton, {Ronald L.} and {Van Meter}, Timothy and Carlotti, {Carlos G.} and Frederick Boop and Darrell Bigner and Gilbertson, {Richard J.} and Rutka, {James T.} and Taylor, {Michael D.}",
note = "Funding Information: We thank the individuals and families who agreed to take part in these studies. We thank S. Egan, J. Ellis and R. Bremner for critical review of the manuscript. We thank R. Wechsler-Reya (Duke), A.M. Kenney (Memorial-Sloan Kettering) and D. Rowitch (University of California San Francisco) for reagents and helpful discussions. We are grateful to K. Helin (University of Copenhagen) for providing JMJD2C expression constructs. We thank P. Paroutis for artwork and S. Archer for editing. We are grateful to C. Marshall and J. Wei for assistance with copy number analysis. This work was supported by the Canadian Cancer Society and the Pediatric Brain Tumor Foundation. M.D.T. is supported by a Sontag Foundation Distinguished Scholar award. Additional research support was obtained from the Hospital for Sick Children Foundation, The Neurosurgery Research and Education Foundation, BRAINCHILD, the 407 Express Toll Route, and the Walker family. M.D.T. was supported by the Laurie Berman fund in Brain Tumor Research, the American Brain Tumor Association and a Clinician-Scientist award from the Canadian Institutes of Health Research. P.A.N. was supported by a Restracomp salary award from the Hospital for Sick Children.",
year = "2009",
month = apr,
doi = "10.1038/ng.336",
language = "English (US)",
volume = "41",
pages = "465--472",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "4",
}