The genome as a record of environmental exposure.
The genome as a record of environmental exposure.
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DOI：
10.1093/mutage/gev073
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发表时间：
2015-11
期刊：
影响因子：
2.7
通讯作者：
Phillips DH
中科院分区：
文献类型：
--
作者：
Nik-Zainal S;Kucab JE;Morganella S;Glodzik D;Alexandrov LB;Arlt VM;Weninger A;Hollstein M;Stratton MR;Phillips DH
人类肿瘤的全基因组测序揭示了不同的突变模式，暗示了癌症的病因。环境诱变剂引起的突变和突变谱的实验研究传统上集中在单个基因上。随着更快更便宜的测序平台的出现，现在可以在整个基因组的实验模型中评估突变谱。作为原理的证明，我们已经检查了暴露于苯并[a]芘（BaP），紫外线（UV）和马兜铃酸（AA）后永生化的小鼠胚胎成纤维细胞的全基因组突变谱。结果表明，每种诱变剂均诱导特征性突变特征：BaP主要为G→T突变，UV主要为C→T和CC→TT突变，AA主要为A→T突变。这些数据不仅与现有知识一致，而且还提供了更高水平的基因组组织的额外信息。该方法有望识别导致人类肿瘤突变的药物，并揭示人类癌症的病因。
Whole genome sequencing of human tumours has revealed distinct patterns of mutation that hint at the causative origins of cancer. Experimental investigations of the mutations and mutation spectra induced by environmental mutagens have traditionally focused on single genes. With the advent of faster cheaper sequencing platforms, it is now possible to assess mutation spectra in experimental models across the whole genome. As a proof of principle, we have examined the whole genome mutation profiles of mouse embryo fibroblasts immortalised following exposure to benzo[a]pyrene (BaP), ultraviolet light (UV) and aristolochic acid (AA). The results reveal that each mutagen induces a characteristic mutation signature: predominantly G→T mutations for BaP, C→T and CC→TT for UV and A→T for AA. The data are not only consistent with existing knowledge but also provide additional information at higher levels of genomic organisation. The approach holds promise for identifying agents responsible for mutations in human tumours and for shedding light on the aetiology of human cancer.