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Nature:与癌症有关的突变

发表时间:2010-08-16  |  阅读次数:21次  |  字体大小 [ ]

对超过400个乳腺癌、肺癌、卵巢癌和前列腺癌样品所做的一项大规模遗传分析,识别出了数千个与癌症相关的突变。Kan等人分析了来自癌症患者的DNA,识别出了涉及1507个编码基因的2576个体突变。

在这些突变中,77个被认为是显着的突变,说明它们可能具有致病作用,包括蛋白激酶、G蛋白耦合的受体和其他潜在治疗目标。(转自:生物谷Bioon.com)


生物谷推荐原文出处:

Nature doi:10.1038/nature09208

Diverse somatic mutation patterns and pathway alterations in human cancers
Zhengyan Kan,Bijay S. Jaiswal,Jeremy Stinson,Vasantharajan Janakiraman,Deepali Bhatt,Howard M. Stern,Peng Yue,Peter M. Haverty,Richard Bourgon,Jianbiao Zheng,Martin Moorhead,Subhra Chaudhuri,Lynn P. Tomsho,Brock A. Peters,Kanan Pujara,Shaun Cordes,David P. Davis,Victoria E. H. Carlton,Wenlin Yuan,Li Li,Weiru Wang,Charles Eigenbrot,Joshua S. Kaminker,David A. Eberhard,Paul Waring,Stephan C. Schuster,Zora Modrusan,Zemin Zhang,David Stokoe,Frederic J. de Sauvage, Malek Faham & Somasekar Seshagiri et al.

The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics1. Here we report the identification of 2,576 somatic mutations across ~1,800?megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes. Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets. Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for gα subunits in multiple cancer types. Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Gα subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis. Our study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.

 

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