Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair.
Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair.
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DOI：
10.1038/nbt.2778
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发表时间：
2014-01
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
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癌症的发生和肿瘤进展是由体细胞突变的积累所介导的。在这里，我们报告了癌症基因组中体细胞突变的局部密度高度降低，特别是在由DNase I超敏部位定义的可访问的调控DNA中。这种减少与任何已知的影响体细胞突变密度的因素无关，并在不同的癌症类型中观察到，这表明了一种一般的机制。通过对单个癌症基因组的分析，我们表明，调控DNA中局部突变密度的降低与完整的全球基因组修复机制有关，在具有多核苷酸切除修复组件突变的个别癌症中，突变现象几乎完全消除。总之，我们的结果将染色质结构、基因调控和与癌症相关的体细胞突变联系在一起。
Carcinogenesis and neoplastic progression are mediated by the accumulation of somatic mutations. Here we report that the local density of somatic mutations in cancer genomes is highly reduced specifically in accessible regulatory DNA defined by DNase I hypersensitive sites. This reduction is independent of any known factors influencing somatic mutation density and is observed in diverse cancer types, suggesting a general mechanism. By analyzing individual cancer genomes, we show that the reduced local mutation density within regulatory DNA is linked to intact global genome repair machinery, with nearly complete abrogation of the hypomutation phenomenon in individual cancers that possess mutations in multiple nucleotide excision repair components. Together, our results connect chromatin structure, gene regulation and cancer-associated somatic mutation.
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影响因子：
14.9
作者：
Haruta N;Kubota Y;Hishida T
通讯作者：
Hishida T
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Fei J;Kaczmarek N;Luch A;Glas A;Carell T;Naegeli H
通讯作者：
Naegeli H
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.