The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes.
The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes.
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DOI：
10.1038/ncomms4630
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发表时间：
2014-04-08
影响因子：
16.6
通讯作者：
Downing, James R.
中科院分区：
文献类型：
--
作者：
Huether, Robert;Dong, Li;Chen, Xiang;Wu, Gang;Parker, Matthew;Wei, Lei;Ma, Jing;Edmonson, Michael N.;Hedlund, Erin K.;Rusch, Michael C.;Shurtleff, Sheila A.;Mulder, Heather L.;Boggs, Kristy;Vadordaria, Bhavin;Cheng, Jinjun;Yergeau, Donald;Song, Guangchun;Becksfort, Jared;Lemmon, Gordon;Weber, Catherine;Cai, Zhongling;Dang, Jinjun;Walsh, Michael;Gedman, Amanda L.;Faber, Zachary;Easton, John;Gruber, Tanja;Kriwacki, Richard W.;Partridge, Janet F.;Ding, Li;Wilson, Richard K.;Mardis, Elaine R.;Mullighan, Charles G.;Gilbertson, Richard J.;Baker, Suzanne J.;Zambetti, Gerard;Ellison, David W.;Zhang, Jinghui;Downing, James R.
在这里，我们对1000多个儿科肿瘤中编码大多数已知表观遗传调节蛋白的633个基因进行测序，以确定儿科癌症表观遗传调节因子的体细胞突变情况。我们的研究结果表明，在21种不同的儿科癌症亚型中，基因突变频率存在显著差异，在高级别胶质瘤、T系急性淋巴细胞白血病、髓母细胞瘤中检测到的突变频率最高，在低级别胶质瘤和视网膜母细胞瘤中检测到的突变频率很少。最常见的突变基因是H3F3A、PHF 6、ATRX、KDM6A、SMARCA 4、ASXL2、CREBBP、EZH2、MLL2、USP 7、ASXL1、NSD 2、SET D2、SMC1A和ZMYM 3。重要的是，我们确定了儿童白血病中泛素特异性加工蛋白酶7（USP7）的新型功能丧失突变，这导致去泛素化活性降低。总的来说，我们的研究结果有助于确定儿科癌症中表观遗传调控基因突变的情况，并为研究表观遗传失调在癌症中的作用提供了一个有价值的新数据库。
Here we sequence 633 genes, encoding the majority of known epigenetic regulatory proteins, in over 1000 pediatric tumors to define the landscape of somatic mutations in epigenetic regulators in pediatric cancer. Our results demonstrate a marked variation in the frequency of gene mutations across 21 different pediatric cancer subtypes, with the highest frequency of mutations detected in high-grade gliomas, T-lineage acute lymphoblastic leukemia, 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. Importantly, we identify novel loss-of-function mutations in the ubiquitin-specific-processing protease 7 (USP7) in pediatric leukemia, which result in a decrease in deubiquitination activity. Collectively, our results help to define the landscape of mutations in epigenetic regulatory genes in pediatric cancer and yield a valuable new database for investigating the role of epigenetic dysregulations in cancer.
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影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
30.8
作者：
Holmfeldt, Linda;Wei, Lei;Diaz-Flores, Ernesto;Walsh, Michael;Zhang, Jinghui;Ding, Li;Payne-Turner, Debbie;Churchman, Michelle;Andersson, Anna;Chen, Shann-Ching;McCastlain, Kelly;Becksfort, Jared;Ma, Jing;Wu, Gang;Patel, Samir N.;Heatley, Susan L.;Phillips, Letha A.;Song, Guangchun;Easton, John;Parker, Matthew;Chen, Xiang;Rusch, Michael;Boggs, Kristy;Vadodaria, Bhavin;Hedlund, Erin;Drenberg, Christina;Baker, Sharyn;Pei, Deqing;Cheng, Cheng;Huether, Robert;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda L.;Tabib, Yashodhan;Dooling, David J.;Ochoa, Kerri;Minden, Mark;Lewis, Ian D.;To, L. Bik;Marlton, Paula;Roberts, Andrew W.;Raca, Gordana;Stock, Wendy;Neale, Geoffrey;Drexler, Hans G.;Dickins, Ross A.;Ellison, David W.;Shurtleff, Sheila A.;Pui, Ching-Hon;Ribeiro, Raul C.;Devidas, Meenakshi;Carroll, Andrew J.;Heerema, Nyla A.;Wood, Brent;Borowitz, Michael J.;Gastier-Foster, Julie M.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Downing, James R.;Hunger, Stephen P.;Loh, Mignon L.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
预测蛋白质突变的功能影响：在癌症基因组学中的应用。
影响因子：
14.9
作者：
Reva B;Antipin Y;Sander C
通讯作者：
Sander C
影响因子：
64.5
作者：
Hu, M;Li, PW;Shi, YG
通讯作者：
Shi, YG