单击和多击PIK3CA短变体基因组改变在临床晚期前列腺癌:一个基因组景观研究
Michael F Basin1, Carla M Miguel1, Joseph M Jacob1
1Department of Urology, Upstate Medical University, 750 East Adams St., Syracuse, NY, 13210, USA.
Targeted oncology
|October 5, 2024
概括
晚期前列腺癌中多次受到PIK3CA的改变与更多的驱动基因组改变有关,并可能预测对向治疗的反应. 这一发现支持针对PIK3CA向治疗的新临床试验设计.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 癌症治疗方法 癌症治疗方法
背景情况:
- 多次击中PIK3CA突变与接受抗PIK3CA疗法治疗的乳腺癌患者的更好的结果相关.
- 晚期前列腺癌中多次撞击PIK3CA变化的基因组概况和临床相关性尚不清楚.
研究的目的:
- 调查临床晚期前列腺癌 (CAPC) 中单击和多击PIK3CA基因组改变的基因组景观.
主要方法:
- 利用FoundationCore数据库分析了来自19,978个CAPC瘤的综合基因组分析数据.
- 评估了所有类型的基因组改变 (GA),瘤突变负担 (TMB),微卫星不稳定性 (MSI) 和同源重组缺陷 (HRD) 签名.
- 通过免疫组织化学 (IHC) 确定PD-L1表达.
主要成果:
- 在0.4%的CAPC瘤中发现了多次打击的PIK3CA变化,而在5.8%的单次打击中发现了变化.
- 与PIK3CA野生型瘤相比,单击和多击PIK3CA变化与更多的驱动GA,更高的TMB以及MMR突变特征和MSI高状态的患病率增加有关.
- 具体的同时发生的GAs包括BRCA2和ATM在多击PIK3CA病例中,以及PTEN在单击病例中. 在PIK3CA野生型瘤中,HRD特征更高.
结论:
- 在CAPC中存在多次PIK3CA基因组变化的存在表明了独特的瘤表型.
- 这种表型可能表明对抗PIK3CA向疗法和检查点抑制剂的敏感性.
- 这些发现支持在CAPC中研究这些向治疗的临床试验的设计.
相关概念视频
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