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临床综合征与MCM8和MCM9的双性生殖系变异相关
Noah C Helderman1, Ting Yang2, Claire Palles3
1Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
HGG advances
|July 20, 2025
概括
在MCM9中双变异与多重症,胃癌和早期结直肠癌 (CRC) 有关. 两种MCM8和MCM9变种都与阴性腺和早期生殖细胞瘤有关,建议将其纳入遗传检测和监测.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- MCM8和MCM9基因与癌症倾向,多重症,早期发病的癌症和阴性腺癌有关.
- 与MCM8/MCM9变异相关的临床表现和癌症风险的全部范围仍然不清楚.
研究的目的:
- 描述具有双生殖系MCM8/MCM9变异的个体的分子和临床特征.
- 为了澄清这些变体的癌症风险和表型关联.
主要方法:
- 对10万个基因组项目的数据集进行分析,以确定有息肉和癌症的个体中双性MCM9变异的丰富性.
- 分析英国生物库对MCM8变异的数据集.
- 一个26个MCM8和28个MCM9变种携带者的病例系列的临床和分子特征.
主要成果:
- 在10万个基因组项目中,在患有结肠多,直肠多和胃癌的个体中发现的双性MCM9变异的显著丰富.
- 在任何数据集中都没有观察到双基MCM8变体的类似丰富.
- 病例系列证实了MCM9载体的多症,胃癌和早期发病的CRC,并且在MCM8和MCM9载体中确定了早期发病的生殖细胞瘤 (15岁之前),此外还发现了阴性腺癌.
结论:
- 双性MCM9变异与多重症,胃癌和早期的CRC有关.
- 双性MCM8和MCM9两种变体都与低子腺症和早期发病的生殖细胞瘤有关.
- 在特定临床场景的诊断基因组中应考虑MCM8/MCM9基因,携带者可能从癌症监测中受益.
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