在单细胞水平的结直肠癌中瘤内部多样化
Sophie F Roerink1, Nobuo Sasaki2,3, Henry Lee-Six1
1Cancer Ageing and Somatic Mutations Programme, Wellcome Trust Sanger Insitute, Hinxton, UK.
Nature
|April 13, 2018
概括
结肠直肠癌细胞的多样化明显超过正常细胞, 获得许多突变和不同的生物状态. 这种瘤内部异质性会影响药物反应,突出癌症
科学领域:
- 癌症生物学
- 基因组学
- 表观遗传学
背景情况:
- 癌症起源于单个细胞, 但演变为异构的群体.
- 了解瘤内部多样化对于有效的癌症治疗至关重要.
研究的目的:
- 研究结直肠瘤中的遗传和表型多样化.
- 为了比较癌细胞和正常细胞之间的体质突变率和表观遗传状态.
- 评估瘤内异质性对药物反应的影响.
主要方法:
- 从单个结直肠癌细胞和相邻的正常组织中获得的器官的特征.
- 全基因组测序以确定体质突变.
- 对DNA甲基化和转录组状态的分析.
- 评估单细胞衍生器官的药物反应差异.
主要成果:
- 结直肠癌细胞表现出广泛的突变多样化,体内突变明显多于正常细胞.
- 大多数突变都发生在后期的克隆扩张过程中,由不同的突变过程驱动.
- 观察到DNA甲基化和转录组状态的瘤内部异质性,与癌症原型相关.
- 来自同一瘤的密切相关的癌细胞在药物敏感性上表现出明显的差异.
结论:
- 与正常细胞相比,结肠直肠癌细胞的体质突变率显著增加.
- 基因多样化伴随着细胞状态的稳定,可遗传的差异.
- 瘤内部异质性导致药物反应变化,对治疗构成挑战.
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