在APOBEC3A/B选择下癌症相关基因的可变性
Joon-Hyun Song1,2, Liliana M Dávalos3,4, Thomas MacCarthy1,2
1Stony Brook Cancer Center, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, USA.
bioRxiv : the preprint server for biology
|December 18, 2023
概括
APOBEC3酶通过增加基因变异来驱动癌症的进化,特别是在早期癌症中. 它们的突变模式在癌症基因和正常基因之间有所不同,塑造了瘤异质性.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 进化生物学 进化生物学
背景情况:
- 可变性是癌症的一个关键标志,由瘤内异质性和遗传变异驱动.
- 在APOBEC3中,cytidine deaminases会产生突变,在早期癌症阶段会产生重大影响.
- APOBEC活动在塑造基因组进化模式中的确切作用及其对癌症相关基因的差异性影响在很大程度上是未知的.
研究的目的:
- 研究APOBEC3活动如何影响人类基因组内的基因的进化模式.
- 确定APOBEC活动对癌症相关基因与非癌症基因的影响差异.
- 探索APOBEC3基因与癌症发展有关的进化轨迹.
主要方法:
- 对超过4万个人类蛋白质编码转录的分析,以确定APOBEC3A/BTC模式分布模式.
- 在一个具有扩展APOBEC3谱的蝙蝠物种中对APOBEC3基因正义的比较分析.
- 计算模拟以建模APOBEC诱导的异质性对癌症进化和克隆动态的影响.
主要成果:
- 在人类的癌症相关基因和控制基因之间观察到明显的APOBEC3A/BTC动机分布模式.
- 与对照组相比,蝙蝠癌症基因的正义基因显示出不同的APOBEC3图案模式,反映了人类的发现.
- 模拟表明,APOBEC诱导的异质性通过在特定基因类中双模引入突变来增强癌症进化.
结论:
- 通过引入遗传变异,APOBEC3活动显著影响癌症的演变.
- 不同的动图分布表明,APOBEC活动与癌症基因之间存在特定的关联.
- APOBEC3基因的进化可能是由于需要减轻它们对宿主基因组的影响,而不是相反,最终导致癌症异质性.
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