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对膀瘤中几种常见的APOBEC型突变的分析表明与病毒感染有关
Nina Rao1,2, Gabriel J Starrett3, Mary L Piaskowski3
1Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
Cancer prevention research (Philadelphia, Pa.)
|July 21, 2023
概括
吸烟和BK多瘤病毒 (BKPyV) 感染与明显的膀瘤突变有关. 了解这些原因可能会为膀癌的新预防和治疗策略提供信息.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 病毒学 病毒学
背景情况:
- 在膀瘤中,FGFR3和PIK3CA基因突变很常见.
- 反复发生的突变可能源于常见的暴露,如吸烟或病毒感染.
研究的目的:
- 调查吸烟,BK多瘤病毒 (BKPyV) 感染和膀癌中的特定FGFR3/PIK3CA突变之间的联系.
- 探索病毒感染在膀瘤发生中的作用.
主要方法:
- 分析了来自2816个膀瘤的突变数据.
- 用于病毒检测的RNA测序和免疫组织化学 (IHC) (BKPyV).
- 统计分析以将突变与吸烟状态,病毒存在和瘤进展相关联.
主要成果:
- 在吸烟者中,FGFR3-Y375C突变更常见.
- 在从不吸烟者中,APOBEC类型突变 (FGFR3-S249C,PIK3CA-E542K/E545K) 增强.
- 在4.5%的非肌肉侵入性膀癌 (NMIBC) 中检测到BKPyV,但在肌肉侵入性膀癌 (MIBC) 中很少检测到.
- 具有PyV阳性的NMIBC瘤显示出更高的APOBEC型突变患病率和更高的进展风险.
结论:
- 吸烟与FGFR3-Y375C突变有关.
- BKPyV感染可能会导致APOBEC型突变和膀癌的进展,特别是在NMIBC中.
- 清晰的分子机制将吸烟和BKPyV与膀瘤发生联系起来.
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