成年人扩散性质瘤的纵向分子轨迹
Floris P Barthel1,2, Kevin C Johnson1, Frederick S Varn1
1The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Nature
|November 22, 2019
概括
质瘤进化表明,驱动基因在复发时被保留,治疗对瘤发育有随机的影响. 在复发性质瘤中,获得的质积分和亚克隆选择与较差的结果相关.
科学领域:
- 癌症学
- 遗传学
- 进化生物学
背景情况:
- 扩散性质瘤的治疗耐药性是一个重大的临床挑战.
- 了解质瘤的进化动态对于开发有效治疗至关重要.
研究的目的:
- 研究从初始诊断到复发的扩散性质瘤的演变轨迹.
- 确定导致质瘤演变和治疗耐药性的遗传变化和选择性压力.
主要方法:
- 对222名成年质瘤患者的DNA测序数据和临床注释进行了分析.
- 在初始和复发阶段对质瘤亚型的突变,副本数量变化和克隆结构进行比较分析.
- 评估包括基化剂在内的治疗对瘤进化和患者生存的影响.
主要成果:
- 在初始诊断时存在的驱动基因改变在复发时在很大程度上被保留.
- 基化剂治疗诱导过度突变表型,但过度突变没有影响整体存活率.
- 获得的无体积变异,特别是在IDH突变的质瘤中没有1p/19q共删除,与细胞周期的改变和不良结果有关.
- 在瘤进化过程中的亚克隆选择与生存率下降相关.
结论:
- 在扩散性质瘤中最强的选择性压力发生在早期发育过程中.
- 目前的治疗方法似乎在很大程度上是随机的.
- 了解这些进化模式是克服质瘤治疗耐药性的关键.
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