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The mutational signature profile of known and suspected human carcinogens in mice
Nature Genetics ( IF 31.7 ) Pub Date : 2020-09-28 , DOI: 10.1038/s41588-020-0692-4
Laura Riva 1 , Arun R Pandiri 2 , Yun Rose Li 3 , Alastair Droop 1 , James Hewinson 1 , Michael A Quail 1 , Vivek Iyer 1 , Rebecca Shepherd 1 , Ronald A Herbert 2 , Peter J Campbell 1 , Robert C Sills 2 , Ludmil B Alexandrov 4 , Allan Balmain 3 , David J Adams 1
Affiliation  

Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.



中文翻译:


已知和疑似人类致癌物在小鼠体内的突变特征谱



流行病学研究已经发现许多环境因素似乎会显着增加人类患癌症的风险。通过分析长期暴露于 20 种已知或疑似人类致癌物中的一种的小鼠的肿瘤基因组,我们发现大多数药物不会产生明显的突变特征或增加突变负担,大多数突变(包括驱动突变)是由组织特异性内源性过程引起的。我们识别了因接触钴和偏二氯乙烯而产生的特征,并将不同的人类特征(SBS19 和 SBS42)与 1,2,3-三氯丙烷(一种卤代烷烃和饮用水污染物)联系起来,并在人类肿瘤基因组中发现了这些特征和其他特征。我们定义了由与人类健康相关的重要药物纲要诱发的肿瘤的跨物种基因组图谱。

更新日期:2020-09-28
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