在单个瘤基因内多个突变的景观和功能
Yuki Saito1,2, Junji Koya1, Mitsugu Araki3
1Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan.
Nature
|June 5, 2020
概括
同一个癌基因中的多个驱动突变 (MMs) 在癌症中很常见,影响9%的样本. 这些MM增强了瘤性和药物敏感性,揭示了癌症演变的关键机制.
科学领域:
- 基因组学
- 癌症生物学
- 癌症学
背景情况:
- 零星报告显示单个瘤基因中的多个驱动突变 (MMs).
- 癌症中MMs的患病率和意义在很大程度上是未知的.
研究的目的:
- 进行全面的泛癌分析,以确定MM的风景和相关性.
- 研究MMs的突变模式和功能影响.
主要方法:
- 对60,954个癌症样本进行全癌症分析.
- 具有显著频率的MM的癌基因的鉴定.
- 单个与多个突变的突变模式和功能影响的比较分析.
主要成果:
- 确定了14种泛癌和6种癌症类型特异性瘤基因.
- 与单个突变相比,MMs在cis中发生并表现出不同的突变特征 (类型,位置,替代).
- 这种MM涉及功能弱的,不常见的突变组合,使其具有增强的致癌性.
- 在PIK3CA和NOTCH1中具有MM的细胞显示出依赖性,信号和药物敏感性增加.
结论:
- 瘤性MMs是癌症的一个常见的驱动因素.
- 提供罕见,低于最佳突变的克隆选择机制.
- 了解MM对于癌症驱动事件的识别和治疗策略至关重要.
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