生物
索引
DNA损伤
基因组
诱导多能干细胞
计算生物学
DNA修复
突变
人类基因组
DNA
基因
遗传学
胚胎干细胞
单核苷酸多态性
基因型
作者
Jill E. Kucab,Xueqing Zou,Sandro Morganella,Madeleine Joel,Arjun Scott Nanda,Eszter Nagy,Céline Gomez,Andrea Degasperi,Robert G. Harris,Stephen Jackson,Volker M. Arlt,David H. Phillips,Serena Nik-Zainal
出处
期刊:Cell
[Elsevier]
日期:2019-05-01
卷期号:177 (4): 821-836.e16
被引量:410
标识
DOI:10.1016/j.cell.2019.03.001
摘要
Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 WGS human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. Additionally, six agents produced double-substitution signatures and eight produced indel signatures. Investigating mutation asymmetries across genome topography revealed fully functional mismatch and transcription-coupled repair pathways. DNA damage induced by environmental mutagens can be resolved by disparate repair and/or replicative pathways, resulting in an assortment of signature outcomes even for a single agent. This compendium of experimentally induced mutational signatures permits further exploration of roles of environmental agents in cancer etiology and underscores how human stem cell DNA is directly vulnerable to environmental agents.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjNjA0ZmFiYTVmMGU3OGJlMjIwNDk4ODM4OGFiMWI2NSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc5MTUxMjA2fQ.CTKsE0-Qsf5SCdj2dj23SyFaUlM9RUWeWDvQeRJcbYD_IrC4Ljh3yf5CIuqcUECWGEVoEdITYP52wfkJBWH5Cq7HblYZMdL8aGF-57elq89RTe8K0IqOMoBma4Wn9d6ZsD1tsQqFa-6qBraA_pUmQxDqRYHHN9ftW-Ao9Et-lGsYPt3cREhTCBLMYqb_4Ssbu1cKnoU3mASZfGXiQlJxRtTNZllC9S2P7cbRSf9BleSsSGt-XZOAqDvLLuuvsj228-7j9MotR-T9LUteZMivfflp9zFrUk2x5_dIleGBaSbGM0vQMeuRKcb_5LIoSpZyOOG5yVYdNYtUn3I1XiOiqw(mp4, (142.75 MB) Download video
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