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.
iScience
|March 29, 2024
概括
APOBEC3酶通过创造遗传变异来驱动癌症的进化. 它们的突变模式在癌症和非癌症基因之间有所不同,增加了瘤异质性和可变性.
科学领域:
- 遗传学 是一个遗传学.
- 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特征,受遗传变异和瘤内部异质性的影响.
- APOBEC3酶是已知的变异原体,有助于瘤的遗传变异.
- APOBEC3对癌症基因进化与非癌症基因的具体影响尚不清楚.
研究的目的:
- 研究APOBEC3突变对癌症相关基因的差异影响.
- 探索癌症和跨物种的非癌症基因中APOBEC3的进化模式.
- 确定APOBEC3诱导的异质性如何影响癌症基因组进化.
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.
- 在癌症和非癌症基因的蝙蝠体内对APOBEC3基因模式的比较分析.
- 计算模拟以建模APOBEC3诱导的异质性对癌症演变的影响.
主要成果:
- 在人类癌症和非癌症基因之间观察到明显的APOBEC3A/BTC动机分布模式.
- 类似的独特的图案图案在蝙蝠的ortologs中被发现,这表明APOBEC3.3的进化适应.
- 模拟表明,通过双模突变模式,APOBEC3诱导的异质性增强了癌症的演变.
结论:
- APOBEC3酶表现出与癌症基因相关的独特模式分布.
- APOBEC3的进化轨迹可能包括将其对重要基因的影响降到最低.
- APOBEC3诱导突变的双模分布显著促进了癌症异质性和可变性.
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