在患有塞尔托利 - 莱迪格细胞瘤的患者中,内部生殖系DICER1变异
Claudette R Fraire1, Paige R Mallinger2,3,4, Jessica N Hatton5
1Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX.
JCO precision oncology
|October 26, 2023
概括
生殖系DICER1致病性功能丧失变体使个体易患诸如塞尔托利-莱迪格细胞瘤 (SLCT) 等癌症. 在缺乏典型DICER1变异的SLCT患者中发现了影响拼接的新型内部变异,这表明了更广泛的诊断方法.
科学领域:
- 遗传学和瘤学 在
- 分子生物学分子生物学
- 癌症倾向症候群 癌症倾向症候群
背景情况:
- 在DICER1中的生殖系致病性功能丧失 (pLOF) 变异与各种固体瘤有关,包括塞尔托利-莱迪格细胞瘤 (SLCT).
- 常见的DICER1 pLOF变体包括框架转移的内置和无意义的或拼接位置改变的基底替代.
- 一些患有DICER1相关瘤的患者缺乏可检测的生殖系或瘤pLOF变体.
研究的目的:
- 在没有可检测的生殖系DICER1 pLOF变异的患者中调查SLCT的遗传基础.
- 为了识别可能导致瘤发生的新型DICER1变异.
- 评估内部变异和拼接分析在诊断DICER1相关癌症中的有用性.
主要方法:
- 瘤测序在两个患有SLCT的患者身上进行.
- 进行了常规的exon导向生殖系测序.
- 一个定制的捕获面板被用于全面的DICER1变体分析,包括内部区域.
- 进行了拼接分析,以评估已识别的变异的功能影响.
主要成果:
- 两个患有SLCT的患者在瘤中只存在体质错觉DICER1 RNase IIIb变异.
- 通过常规测序检测,这些患者的生殖系中没有检测到外来pLOF变异.
- 使用自定义捕获面板识别了影响DICER1拼接的新型内基变异 (c.1752+213A>G和c.1509+16A>G).
结论:
- 身体错误的DICER1变体和影响拼接的新型内在变体可能会导致SLCT的发展.
- 传统的生殖线测序可能会错过患有DICER1相关瘤的患者的致病性DICER1变异.
- 在没有发现外源DICER1 pLOF变异的情况下,尽管对DICER1相关癌症有强烈的临床怀疑,但建议进行内部测序和拼接分析.
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