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Diverse somatic mutation patterns and pathway alterations in human cancers

机译：人类癌症中的多种体细胞突变模式和途径改变

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The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics. 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 Ga subunits in multiple cancer types.Furthermore,our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Ga 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.
机译：癌症基因组中体细胞突变的系统表征对于理解疾病和开发靶向治疗药物至关重要。在这里，我们报告了在约1800兆碱基的DNA中鉴定到2576个体细胞突变，这些DNA代表来自441种肿瘤的1507个编码基因，包括乳腺癌，肺癌，卵巢癌和前列腺癌的类型和亚型。我们发现，突变率和突变基因集在肿瘤类型和亚型之间有很大差异。统计分析确定了77个显着突变的基因，包括蛋白激酶，G蛋白偶联受体，例如GRM8，BAI3，AGTRL1（也称为APLNR）和LPHN3，以及其他可药物靶向。体细胞突变和拷贝数变化的综合分析确定了包括GNAS在内的另外35个显着改变的基因，表明Ga亚基在多种癌症类型中的作用得到了扩展。此外，我们的实验分析证明了突变GNAO1（一个Ga亚基）和突变MAP2K4的功能作用。 （JNK信号通路的成员）在肿瘤发生中。我们的研究概述了主要人类癌症的突变谱，并确定了几种潜在的治疗靶标。

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  • 来源
    《Nature》 |2010年第7308期|P.869-873ⅴ|共6页
  • 作者

    Zhengyan Kan; Bijay S. Jaiswal; Jeremy Stinson; Vasantharajan Janakiraman; Deepali Bhatt; et al;

  • 作者单位

    Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    rnDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    rnDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    rnDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    rnDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA;

    rn;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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