跨癌症类型的PIK3CA异常的患病率和临床影响:现实世界的下一代测序方法
Junkyu Kim1, Hye-Lim Jang2, Jung Young Hong1
1Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
Cancer genetics
|July 19, 2025
概括
在3886名患者中,PIK3CA突变在9.2%的患者中被发现,特别是结直肠癌患者. 这些突变与较高的瘤突变负担和微卫星不稳定性相关,为PIK3CA驱动的固体瘤提供了洞察力.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 由于PIK3CA基因的改变,酸-3-酶 (PI3K) 途径在癌症中经常被激活.
- 虽然PIK3CA突变乳腺癌显示治疗效果,但其他恶性瘤缺乏向治疗.
- 了解不同癌症类型的PIK3CA突变和放大是至关重要的.
研究的目的:
- 在一大群患有各种固体瘤的患者中调查PIK3CA突变和放大发生率和频谱.
- 探索PIK3CA异常与关键生物标记物,如瘤突变负担 (TMB),微卫星不稳定性 (MSI) 和同源重组缺陷 (HRD) 之间的相关性.
主要方法:
- 使用Trusight Oncology 500的下一代测序 (NGS) 对36种癌症类型的3886名患者进行了测序.
- 数据分析包括PIK3CA突变和放大发生率,它们按癌症类型的分布,以及与TMB,MSI和HRD的关联.
- 确定了特定的突变部位.
主要成果:
- 在9.2% (358/3886) 的患者中检测到PIK3CA突变,结直肠癌 (52.8%) 的患病率最高.
- 与没有PIK3CA突变的患者相比,PIK3CA突变的患者表现出明显更高的TMB (31.8%对12.5%) 和MSI高率 (7.8%对1.6%) (p=0.001).
- PIK3CA放大发生在1.3%的患者中 (51/3886),主要发生在胃癌,膀癌和结直肠癌中,并且与较低的TMB,高MSI和HRD率有关. 常见的突变部位包括E545K,E542K和H1047R.
结论:
- 这项研究提供了转移性实体瘤中PIK3CA异常的全面概述,识别了频繁的突变 (9.2%) 和放大 (1.3%).
- NGS分析显示,PIK3CA突变与增加TMB/MSI高状态之间存在显著的关联.
- 这些发现提高了对各种癌症中PIK3CA变化的理解,并可能指导未来的治疗策略.
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