基因和转录进化改变了癌细胞的药物反应
Uri Ben-David1, Benjamin Siranosian1, Gavin Ha1,2
1Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Nature
|August 10, 2018
概括
人类癌细胞系由于培养进化而表现出显著的遗传多样性. 这种异质性影响了药物反应,突显了癌症研究中需要仔细的表征.
科学领域:
- 基因组学
- 癌症生物学
- 细胞异质性
背景情况:
- 人类癌细胞系是研究的重要工具.
- 细胞系进化及其后果尚未完全理解.
- 细胞系中的遗传和转录异质性需要进一步研究.
研究的目的:
- 研究人类癌细胞系中的遗传和转录异质性的程度和起源.
- 了解细胞系进化的功能后果,包括药物反应.
- 为测量细胞系变异提供框架,以提高研究可重复性.
主要方法:
- 在两个实验室对106个人类癌细胞系进行基因组分析.
- 27种MCF7乳腺癌细胞系的综合基因组特征.
- 条码实验和单细胞克隆分析以研究细胞系进化.
- 对321种抗癌化合物的MCF7菌株的药物反应测试.
主要成果:
- 在包括MCF7在内的人类癌细胞系中观察到大量的克隆多样性和快速的遗传多样化.
- 基因变化与改变的基因表达,细胞形态和增殖相关.
- 细胞系进化是由对培养条件敏感的阳性克隆选择驱动的.
- 在细胞系菌株之间发现了抗癌药物反应的显著差异,高达75%的化合物表现出不同的疗效.
结论:
- 人类癌细胞系由于培养中的进化过程而表现出大量的遗传变异和异质性.
- 这种异质性显著影响功能结果,特别是药物反应.
- 研究人员需要考虑和测量细胞系变异,以确保可复制和可靠的癌症研究.
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