遗传背景导致混合人群肺癌的体细胞突变。
Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
出版信息
Cancer Discov. 2021 Mar;11(3):591-598. doi: 10.1158/2159-8290.CD-20-1165. Epub 2020 Dec 2.
Abstract
Inherited lung cancer risk, particularly in nonsmokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden, and specific driver mutations in , and . A local Native American ancestry risk score was more strongly correlated with mutation frequency compared with global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities. SIGNIFICANCE: The frequency of somatic and mutations in lung cancer varies by ethnicity, but we do not understand why. Our study suggests that the variation in and mutation frequency is associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association...
摘要
遗传性肺癌风险，尤其是在不吸烟者中，目前仍了解甚少。对来自拉丁美洲的 1153 例肺癌进行的基因组和祖源分析显示，美洲原住民祖源与肿瘤突变负荷以及 、 中的特定驱动突变之间存在显著关联。与全球祖源相关性相比，局部美洲原住民祖源风险评分与 突变频率的相关性更强，这表明这些差异的基础是种系遗传学（而不是环境暴露）。意义：肺癌中体细胞 和 突变的频率因种族而异，但我们不知道原因。我们的研究表明， 和 突变频率的变化与遗传祖源有关，并建议进一步研究以确定构成这种关联的种系等位基因。
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