• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The mutation spectrum revealed by paired genome sequences from a lung cancer patient
【24h】

The mutation spectrum revealed by paired genome sequences from a lung cancer patient

机译：肺癌患者基因组序列配对揭示的突变谱

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60× coverage) and adjacent normal tissue (46×). Comparing the two genomes, we identify a wide variety of somatic variations, including > 50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilo-bases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.
机译：肺癌是全球范围内与癌症相关的死亡率的主要原因，吸烟者中的非小细胞肺癌是该疾病的主要形式。尽管先前的研究已经确定了肺癌中重要的常见体细胞突变，但它们主要集中在有限的一组基因上，因此提供了突变谱的受限视图。最近的癌症测序工作已使用下一代测序技术来提供白血病，乳腺癌和癌细胞系中突变的全基因组视图。在这里，我们介绍原发性肺肿瘤（覆盖率60倍）和邻近正常组织（46倍）的完整序列。比较这两个基因组，我们发现了各种各样的体细胞变异，包括> 50,000个高可信度的单核苷酸变异。我们验证了这种肿瘤中的530个体细胞单核苷酸变异体，包括KRAS原癌基因中的一个，编码区域中的391个，以及43个大规模结构变异。这些构成了大量新的体细胞突变，估计每兆碱基全基因组范围的体细胞突变率约为17.7。值得注意的是，与未表达的基因相比，我们观察到针对表达的基因中的突变进行选择的独特模式，并且在所有蛋白质编码基因上游最多5千个碱基的启动子区域中。此外，我们观察到激酶基因中氨基酸改变突变的发生率更高。我们提出了单个肺肿瘤中体细胞变化的全面观点，并据我们所知提供了肿瘤环境内存在的独特选择性压力的第一个证据。

著录项

  • 来源
    《Nature》 |2010年第7297期|p.473-477|共5页
  • 作者

    William Lee; Zhaoshi Jiang; Jinfeng Liu; Peter M. Haverty; Yinghui Guan; Jeremy Stinson; Peng Yue; Yan Zhang; Krishna P. Pant; Deepali Bhatt; Connie Ha; Stephanie Johnson; Michael I. Kennemer; Sankar Mohan; Igor Nazarenko; Colin Watanabe; Andrew B. Sparks; David S. Shames; Robert Gentleman; Frederic J. de Sauvage; Howard Stern; Ajay Pandita; Dennis G. Ballinger; Radoje Drmanac; Zora Modrusan; Somasekar Seshagiri; Zemin Zhang;

  • 作者单位

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Pathology, Genentech Inc., South San Francisco, California 94080, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Department of Oncology Diagnostics, Genentech Inc., South San Francisco, California 94080, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Department of Oncology Diagnostics, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Pathology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Oncology Diagnostics, Genentech Inc., South San Francisco, California 94080, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Complete Genomics Inc., Mountain View, California 94043, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA;

    Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号