| Literature DB >> 24710217 |
Robert Huether1, Li Dong2, Xiang Chen3, Gang Wu3, Matthew Parker3, Lei Wei3, Jing Ma4, Michael N Edmonson3, Erin K Hedlund3, Michael C Rusch3, Sheila A Shurtleff4, Heather L Mulder5, Kristy Boggs5, Bhavin Vadordaria5, Jinjun Cheng4, Donald Yergeau5, Guangchun Song4, Jared Becksfort3, Gordon Lemmon3, Catherine Weber4, Zhongling Cai4, Jinjun Dang4, Michael Walsh6, Amanda L Gedman4, Zachary Faber4, John Easton5, Tanja Gruber7, Richard W Kriwacki8, Janet F Partridge9, Li Ding10, Richard K Wilson10, Elaine R Mardis10, Charles G Mullighan4, Richard J Gilbertson11, Suzanne J Baker11, Gerard Zambetti9, David W Ellison4, Jinghui Zhang3, James R Downing4.
Abstract
Studies of paediatric cancers have shown a high frequency of mutation across epigenetic regulators. Here we sequence 633 genes, encoding the majority of known epigenetic regulatory proteins, in over 1,000 paediatric tumours to define the landscape of somatic mutations in epigenetic regulators in paediatric cancer. Our results demonstrate a marked variation in the frequency of gene mutations across 21 different paediatric cancer subtypes, with the highest frequency of mutations detected in high-grade gliomas, T-lineage acute lymphoblastic leukaemia and medulloblastoma, and a paucity of mutations in low-grade glioma and retinoblastoma. The most frequently mutated genes are H3F3A, PHF6, ATRX, KDM6A, SMARCA4, ASXL2, CREBBP, EZH2, MLL2, USP7, ASXL1, NSD2, SETD2, SMC1A and ZMYM3. We identify novel loss-of-function mutations in the ubiquitin-specific processing protease 7 (USP7) in paediatric leukaemia, which result in decreased deubiquitination activity. Collectively, our results help to define the landscape of mutations in epigenetic regulatory genes in paediatric cancer and yield a valuable new database for investigating the role of epigenetic dysregulations in cancer.Entities:
Mesh：
Year: 2014 PMID： 24710217 PMCID： PMC4119022 DOI： 10.1038/ncomms4630
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919