Analysis of somatic microsatellite indels identifies driver events in human tumors.
Analysis of somatic microsatellite indels identifies driver events in human tumors.
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DOI：
10.1038/nbt.3966
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发表时间：
2017-10
影响因子：
46.9
通讯作者：
Getz, Gad
中科院分区：
文献类型：
--
作者：
Maruvka, Yosef E.;Mouw, Kent W.;Karlic, Rosa;Parasuraman, Prasanna;Kamburov, Atanas;Polak, Paz;Haradhvala, Nicholas J.;Hess, Julian M.;Rheinbay, Esther;Brody, Yehuda;Koren, Amnon;Braunstein, Lior Z.;D'Andrea, Alan;Lawrence, Michael S.;Bass, Adam;Bernards, Andre;Michor, Franziska;Getz, Gad
微卫星（MSs）是短DNA基序的可变长度重复序列，以重复基序的插入或缺失（indels）的形式表现出高突变率。尽管它们普遍存在，但由于在短读测序数据中难以检测到它们，体细胞MS索引对癌症的贡献在很大程度上尚未被探索。在这里，我们提出了两种工具：用于准确检测体细胞MS索引的MSMuTect和用于以高于偶然预期的频率识别含有MS索引的基因的MSMutSig。将MSMuTect应用于代表20种肿瘤类型的6747例人类肿瘤的全外显子组数据，我们在癌症基因中鉴定出了1000个新的MS索引。此外，我们证明了MS索引的数量和模式可以准确区分微卫星稳定（MSS）肿瘤和微卫星不稳定（MSI）肿瘤，这可能会改善临床相关亚群的分类。最后，我们确定了7个新的MS indel驱动热点，其中4个位于已知的癌症基因中（ACVR2A、RNF43、JAK1和MSH3），另外3个位于以前未涉及的癌症驱动基因中（ESRP1、PRDM2和DOCK3）。
Microsatellites (MSs) are tracts of variable-length repeats of short DNA motifs that exhibit high rates of mutation in the form of insertions or deletions (indels) of the repeated motif. Despite their prevalence, the contribution of somatic MS indels to cancer is largely unexplored due to difficulties in detecting them in short-read sequencing data. Here we present two tools: MSMuTect, for accurate detection of somatic MS indels, and MSMutSig, for identification of genes containing MS indels at higher frequency than expected by chance. Applying MSMuTect to whole-exome data from 6,747 human tumors representing 20 tumor types, we identified >1000 novel MS indels in cancer genes. Additionally, we demonstrate that the number and pattern of MS indels can accurately distinguish microsatellite stable (MSS) tumors from tumors with microsatellite instability (MSI), which may improve classification of clinically relevant subgroups. Finally, we identify seven novel MS indel driver hotspots – four in known cancer genes (ACVR2A, RNF43, JAK1, and MSH3) and three in genes not previously implicated as cancer drivers (ESRP1, PRDM2 and DOCK3).
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Biswas, Swati;Trobridge, Patricia;Grady, William M.
通讯作者：
Grady, William M.
影响因子：
3.5
作者：
Kennedy, L;Evans, E;Shelbourne, PF
通讯作者：
Shelbourne, PF