深度分子跟踪超过12年发展的子宫内膜癌从单一患者的增生在一个单一的病人
Katherine Reid1, Olga Camacho-Vanegas2, Deep Pandya3
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA; katherine.reid@mssm.edu.
Cold Spring Harbor molecular case studies
|October 17, 2023
概括
这项研究跟踪了一个患者12年内子宫内膜癌 (EndoCA) 的发展,识别了关键的遗传突变. 孕激素治疗显著降低了导致癌症的PTEN突变水平,为非手术EndoCA管理提供了洞察力.
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:
- 子宫内膜癌 (EndoCA) 是最常见的女性生殖系统恶性瘤.
- 已知从增生症到EndoCA的组织学进展,但在单个患者的这种转变期间的分子变化仍然未被描述.
研究的目的:
- 在单个患者的子宫内膜癌12年发展过程中的分子变化的特征.
- 研究孕激素治疗对这些分子变化的影响.
主要方法:
- 分析了10个连续的子宫内膜活检样本从一个绝经后的女性超过12年.
- 下一代测序使用58个基因面板来识别突变.
- 对关键基因 (包括PTEN和KRAS) 的突变等位基因部分的量化.
主要成果:
- 在七个基因 (APC,ARID1A,CTNNB1,CDKN2A,KRAS,PTEN,TP53) 中发现了八种致病性/可能致病性突变.
- 除正常子宫内膜外,所有样本都存在PTEN无意义突变 (p.W111*),基因分数从良性腺体的0.7%增加到腺癌的36.9%.
- 孕激素治疗始终将PTEN突变等位基因分数降低到癌前水平.
结论:
- 这项研究提供了第一个分子表征的子宫内膜癌的发展在一个病人超过12年的时间.
- 在整个癌症发育过程中观察到持久的PTEN突变.
- 孕激素治疗显示出显著的降低PTEN突变等位基因分数的能力,这表明对子宫内膜癌的非手术治疗有潜力.
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