通过单细胞测序划定三阴性乳腺癌的化学抵抗演变
Charissa Kim1, Ruli Gao2, Emi Sei2
1Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biological Sciences, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Cell
|April 24, 2018
概括
三重阴性乳腺癌 (TNBC) 的化疗耐药性源于先前存在的耐药细胞克隆,而不是新的遗传变化. 这些耐药基因型是通过治疗选择的,而细胞则在化疗期间适应基因表达.
科学领域:
- 癌症学
- 基因组学
- 癌症生物学
背景情况:
- 三重阴性乳腺癌 (TNBC) 是一种常见的化学疗法耐药性的侵袭性亚型.
- 这种抗性的起源 (先前存在的克隆与新突变) 仍然是一个关键的未解决的问题.
研究的目的:
- 研究TNBC中驱动化疗耐药性的机制.
- 将克隆选择和获得的基因组异常作为耐药性的原因进行区分.
主要方法:
- 在接受新辅助化疗 (NAC) 的20名TNBC患者的长度分析.
- 大量外体测序,单细胞DNA测序 (900个细胞) 和单细胞RNA测序 (6862个细胞) 的应用.
主要成果:
- 深层外基因组测序显示,10名患者的克隆消失,10名患者的克隆持续存在.
- 单细胞分析表明,耐药基因型已经存在并由NAC自适应选择.
- 通过细胞重编程来获得转录特征,以应对化疗.
结论:
- 在TNBC中,抗化疗主要是由先前存在的耐药克隆的适应性选择驱动的.
- 细胞重编程和获得的转录特征有助于TNBC的治疗反应和耐药性.
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