马赛克PPM1D突变与患乳腺癌和卵巢癌的倾向有关
Elise Ruark1, Katie Snape, Peter Humburg
1Division of Genetics & Epidemiology, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Nature
|December 18, 2012
概括
在PPM1D基因中罕见的蛋白质截断变异与乳腺和卵巢癌的风险增加有关. 这些马赛克突变可能会导致功能增益效应,影响癌症倾向和管理策略.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 下一代测序的进步使得在常见疾病中研究罕见的遗传变异成为可能.
- 在研究设计,数据分析和罕见变异研究的复制方面存在挑战.
研究的目的:
- 确定与患乳腺癌和卵巢癌的倾向相关的罕见遗传变异.
- 调查已识别的变异的功能影响.
主要方法:
- 在1150个样本中,共聚了507个DNA修复基因的下一代测序.
- 分析策略侧重于蛋白质截断变体 (PTV).
- 在13,642个个体中进行大规模病例对照复制测序.
主要成果:
- 在PPM1D中,罕见的PTV与乳腺癌和卵巢癌倾向有显著的关联.
- 在病例 (25/7,781) 和对照 (1/5,861) 中发现的PPM1D PTV突变.
- 突变是马赛克,聚集在最后的前子中,并导致增强的p53抑制 (功能获取).
结论:
- 罕见的,马赛克PPM1D PTVs增加了乳腺和卵巢癌的风险.
- 突变可能会产生功能增强效应,而不是功能丧失效应.
- 这些发现对癌症风险的检测,管理和理解疾病的罕见/马赛克变异有意义.
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