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瘤进化中的普遍染色体不稳定性和型顺序
Thomas B K Watkins1, Emilia L Lim1,2, Marina Petkovic3
1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nature
|September 4, 2020
概括
染色体不稳定导致癌症的演变, 这项研究揭示了这些变化,体质拷贝数的变化,通常发生并行,并在转移性瘤中丰富.
科学领域:
- 基因组学
- 癌症生物学
- 进化生物学
背景情况:
- 染色体不稳定 (CIN) 通过染色体数量和结构的动态变化驱动癌症的演变.
- 由CIN产生的体内拷贝数变化 (SCNA) 提供了瘤适应和进展的遗传多样性.
研究的目的:
- 研究不同癌症类型中CIN驱动的SCNA异质性的模式和后果.
- 识别反复发生的SCNA事件及其与关键基因组事件 (如全基因组翻倍) 相比的时间.
- 评估转移性瘤中的特定SCNA的丰富性.
主要方法:
- 从22种瘤中对1421个样本进行多样本分期和SCNA分析.
- 对1024个转移样本的独立队列进行分析.
- 在初级与转移环境中对SCNA模式进行比较分析.
主要成果:
- 持续的CIN导致普遍的SCNA异质性,并行进化事件影响了37%的瘤中的关键基因.
- 大多数SCNA损失发生在全基因组倍增之前 (在49%的瘤中发生了克隆性损失),但HLA和8p损失发生在亚克隆性损失之后.
- 在转移样本中丰富了13个焦点SCNA,包括MYC和CCND1放大,表明它们在转移中的作用.
结论:
- 在整个瘤进化过程中,CIN驱动有序,并行的SCNA事件,有助于异质性.
- 在瘤进展和转移过程中选择特定的SCNA,强调它们的功能重要性.
- 了解SCNA模式可以为向治疗提供信息并预测转移潜力.
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