在结直肠癌中,PTEN突变或损失的来源,同时发生和预后值
Ilya G Serebriiskii1,2, Valerii A Pavlov3,4, Grigorii V Andrianov3
1Program in Cell Signaling and Microenvironment, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Ilya.Serebriiskii@fccc.edu.
NPJ genomic medicine
|November 24, 2023
概括
结直肠癌 (CRC) 中的体质PTEN突变显示出复杂的选择压力. 根据瘤亚型和变化类型,PTEN变化具有不同的预后值.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 实体PTEN突变是某些癌症的驱动因素,但在结直肠癌 (CRC) 中很少见.
- 讨论了PTEN改变在CRC侵略性和选择压力的作用.
- 在CRC中,PTEN变化发生的频率很低 (~8-9%).
研究的目的:
- 研究对CRC中PTEN突变的选择压力.
- 确定不同CRC亚型中PTEN变化的预后意义.
- 澄清PTEN在CRC瘤攻击性中的作用.
主要方法:
- 分析了大约53000例CRC病例的基因组数据.
- 检查PTEN突变模式及其与DNA修复和蛋白质功能的相关性.
- 根据微卫星稳定性 (MSS与MSI) 和同时发生的突变 (BRAF,PI3K,TP53) 的分析分层.
主要成果:
- PTEN突变模式表明,DNA依赖性和基于蛋白质功能的选择压力.
- 在微卫星稳定 (MSS) 的CRC中,PTEN变异与BRAF/PI3K突变或TP53缺失同时发生.
- PTEN缺失与MSSCRC的存活率差相关,而PTEN突变与微卫星不稳定 (MSI) CRC的存活率改善相关.
结论:
- 在CRC中的PTEN变化受到复杂的选择压力.
- 在CRC中,PTEN变化具有预后价值,但这取决于瘤亚型 (MSS与MSI) 和变化类型 (突变与删除).
- 驱动器突变格局和PTEN变异类别对于其作为CRC的预后标记的使用至关重要.
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