染色体外瘤基因放大驱动瘤演变和遗传异质性
Kristen M Turner1, Viraj Deshpande2, Doruk Beyter2
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA.
Nature
|February 9, 2017
概括
与正常细胞不同的是,在近一半的人类癌症中发现了外染色体DNA (ecDNA). 这种圆形DNA可以放大瘤基因,加速癌症的演变并增加瘤内异质性.
科学领域:
- 基因组学
- 癌症生物学
- 分子遗传学
背景情况:
- 人类细胞拥有23对染色体.
- 癌症中的基因放大可以发生在染色体或染色体外DNA (ecDNA) 上.
- 癌症中的ecDNA的患病率和功能意义在很大程度上是未知的.
研究的目的:
- 研究人类癌症中的ecDNA的频率和功能重要性.
- 开发一种不偏见的ecDNA检测和分析方法.
- 了解ecDNA在癌症演变中的作用.
主要方法:
- 对来自17种癌症类型的2572个分裂细胞进行全基因组测序和细胞遗传分析.
- 染色体和染色体外DNA的结构建模.
- 开发用于集成ecDNA分析的ECdetect软件包.
主要成果:
- 在近50%的人类癌症中检测到ecDNA,不同瘤类型的频率不同.
- 在正常细胞中很少观察到ecDNA.
- 驱动瘤基因在ecDNA上经常被放大,导致转录水平增加.
- 数学建模和定量分析证实,ecDNA放大比染色体放大更有效地增强瘤基因拷贝数和瘤内异质性.
结论:
- ecDNA是人类癌症的常见特征,对瘤基因放大有显著的贡献.
- 在加速癌症演变和增加瘤内异质性方面,ecDNA起着至关重要的作用.
- 这些发现突出了ecDNA作为癌症治疗的潜在目标.
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