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瘤血统形状与BRCA介导的表型
Philip Jonsson1,2,3, Chaitanya Bandlamudi1, Michael L Cheng4,5
1Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|July 12, 2019
概括
BRCA1和BRCA2基因的生殖基因和体质突变与遗传性癌症有关. 然而,它们的影响因瘤类型而异,有些癌症受益于向治疗,而另一些癌症则显示BRCA突变在生物学上是中立的.
科学领域:
- 遗传学
- 癌症学
- 分子生物学
背景情况:
- 在BRCA1和BRCA2中发生突变会使个体易患遗传性癌症.
- 在BRCA1/ 2突变瘤中,通常会出现DNA修复缺陷和对PARP抑制剂的敏感性增加.
- 在所有癌症类型中,BRCA1/ 2突变的临床和治疗意义尚不清楚.
研究的目的:
- 研究BRCA1/ 2突变在各种癌症类型中的表型和治疗相关性.
- 确定BRCA1/2突变是否是不同瘤系中的创始事件或生物中性事件.
主要方法:
- 在晚期癌症患者中分析BRCA1/ 2的生殖线和体质功能丧失变化.
- 对双基失活,表型透率和PARP抑制敏感性的选择性压力的评估.
- 与BRCA相关的和非BRCA相关的癌症类型的比较.
主要成果:
- 只有在与BRCA相关的癌症类型中观察到选择性压力,表型透率和PARP抑制敏感性.
- 在非BRCA相关的癌症中,瘤发病常常独立于BRCA1/ 2突变.
- 在某些瘤中,BRCA1/2突变是不可或缺的,但在其他瘤中则是生物中性的,这取决于瘤的血统.
结论:
- 瘤血统是BRCA1/2突变的致病作用的一个关键决定因素.
- 这些发现对癌症查,临床试验设计和治疗策略有影响.
- 区分BRCA突变的作用对于个性化癌症治疗至关重要.
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