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A small-cell lung cancer genome with complex signatures of tobacco exposure

机译：具有复杂烟草暴露特征的小细胞肺癌基因组

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摘要

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
机译：癌症是由突变驱动的。在世界范围内，吸烟是导致癌症的主要生活方式，它通过结合并突变DNA的60多种化学物质发挥致癌作用。使用大规模并行测序技术，我们对小细胞肺癌细胞株NCI-H209进行了测序，以探索与吸烟相关的突变负担。总共鉴定出22,910个体细胞取代，包括134个编码外显子。多重突变特征证明了烟草烟雾中致癌物的混合物及其对特定碱基和周围序列背景的倾向。转录偶联修复和第二个更普遍的表达连锁修复途径的影响显而易见。我们确定了串联复制，该复制在框架中复制了CHD7的外显子3-8，以及另外两条携带PVT1-CHD7融合基因的品系，表明CHD7可能在这种疾病中被重新排列。这些发现说明，下一代测序技术有可能为突变过程，细胞修复途径和与癌症相关的基因网络提供空前的见识。

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  • 来源
    《Nature》 |2010年第7278期|184-190|共7页
  • 作者

    Erin D. Pleasance; Philip J. Stephens; Sarah OMeara; David J. McBride; Alison Meynert; et al;

  • 作者单位

    Wellcome Trust Sanger Institute, Hinxton CB10 ISA, UK;

    Wellcome Trust Sanger Institute, Hinxton CB10 ISA, UK;

    Wellcome Trust Sanger Institute, Hinxton CB10 ISA, UK Life Technologies, Warrington WA3 7QH, UK;

    Wellcome Trust Sanger Institute, Hinxton CB10 ISA, UK;

    European Bioinformatics Institute, Hinxton CB10 1SD, UK;

  • 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
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