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局部性前列腺癌的进化格局导致临床攻击性
Shadrielle Melijah G Espiritu1, Lydia Y Liu1, Yulia Rubanova2
1Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, ON M5G 1L7, Canada.
Cell
|April 24, 2018
概括
前列腺癌的演变显示出不同的瘤亚型. 具有多个亚克隆的多克隆瘤的复发率更高,这表明需要积极监测的新生物标志物.
科学领域:
- 癌症学
- 遗传学
- 癌症生物学
背景情况:
- 大多数前列腺癌生长缓慢, 但有些可能会转移致死.
- 了解瘤演变对于预测临床结果至关重要.
研究的目的:
- 在局部性前列腺癌中重建瘤基因.
- 将亚克隆结构与临床结果相关联,并确定关键的遗传事件.
主要方法:
- 对293个局部前列腺瘤的基因重建.
- 对临床结果数据,亚克隆结构和突变特征的分析.
- 在瘤进化过程中发生突变的基因的识别.
主要成果:
- 59% 的患者有多个瘤亚克隆,与不良特征相关.
- 瘤进化从点突变/删除到放大和改变突变特征.
- 特定的基因 (MTOR,NKX3-1,RB1) 被选择性突变.
- 单克隆低风险瘤的复发率低 (7%),而多克隆高风险瘤的复发率高 (61%).
结论:
- 亚克隆结构是前列腺癌复发的重要预测因素.
- 多克隆瘤表明复发的风险更高.
- 具有进化意识的生物标志物可以改善低风险前列腺癌的积极监测策略.
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