环境代理人的突变特征汇编
Jill E Kucab1, Xueqing Zou2, Sandro Morganella3
1Department of Analytical, Environmental and Forensic Sciences, MRC-PHE Centre for Environment and Health, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Cell
|April 16, 2019
概括
环境致癌物会在人体干细胞中引起不同的DNA突变模式. 这项研究确定了特定的突变特征,揭示了细胞修复机制以及人类DNA对环境因素的直接脆弱性.
科学领域:
- 基因组学
- 环境健康
- 癌症研究
背景情况:
- 人体瘤的全基因组测序 (WGS) 揭示了与癌症起源相关的突变模式.
- 了解环境暴露对于识别致癌物质至关重要.
研究的目的:
- 研究暴露于环境致癌物质的人类干细胞的突变特征.
- 描述涉及突变原体引起损伤的DNA修复途径.
主要方法:
- 324个人类诱导的多能干细胞系的全基因组测序 (WGS).
- 干细胞暴露于79种已知或可疑的环境致癌物.
- 对突变特征的分析,包括替代,双替代和插入/删除 (indels).
主要成果:
- 41种致癌物引起了特征性的替代突变特征, 其中一些反映了人类瘤的特征.
- 六个代理商产生了双替代签名,八个代理商产生了独立签名.
- 突变不对称分析证实了功能不匹配和转录合的DNA修复途径.
结论:
- 环境变异原体通过各种修复途径诱导人体干细胞中的多种突变特征.
- 这本摘要有助于探索癌症病因的环境因素.
- 人类干细胞DNA直接受到环境因素的影响.
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