RAD51D基因的c.82G>A（p.Val28Met）变异破坏了正常剪接，并与遗传性卵巢癌相关。
The RAD51D c.82G>A (p.Val28Met) variant disrupts normal splicing and is associated with hereditary ovarian cancer.
作者信息
Yang Ciyu, Arnold Angela G, Catchings Amanda, Rai Vikas, Stadler Zsofia K, Zhang Liying
机构信息
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
出版信息
Breast Cancer Res Treat. 2021 Feb;185(3):869-877. doi: 10.1007/s10549-020-06066-7. Epub 2021 Jan 16.
PURPOSE
Mutations in RAD51D are associated with a predisposition to primary ovarian, fallopian tube, and peritoneal carcinoma. Our study aims to characterize a RAD51D missense variant in a hereditary ovarian cancer family.
METHODS
The effects of the RAD51D c.82G>A (p.Val28Met) variant on mRNA splicing were evaluated and characterized using RT-PCR, cloning and DNA sequencing.
RESULTS
This variant completely disrupts normal splicing and results in the loss of 3'end of 5'UTR and the entire exon 1 (c.-86_c.82), which presumably leads to loss of the RAD51D protein. The RAD51D c.82G>A (p.Val28Met) variant is clinically significant and classified as likely pathogenic.
CONCLUSIONS
Our results indicate that the RAD51D c.82G>A (p.Val28Met) variant contributes to cancer predisposition through disruption of normal mRNA splicing. The identification of this variant in an individual affected with high-grade serous fallopian tube cancer suggests that the RAD51D variant may contribute to predisposition to the ovarian cancer in this family.
目的
RAD51D基因的突变与原发性卵巢癌、输卵管癌和腹膜癌的易感性相关。我们的研究旨在对一个遗传性卵巢癌家族中的RAD51D错义变异进行特征分析。
方法
使用逆转录聚合酶链反应（RT-PCR）、克隆和DNA测序对RAD51D基因c.82G>A（p.Val28Met）变异对mRNA剪接的影响进行评估和特征分析。
结果
该变异完全破坏了正常剪接，导致5'非翻译区（5'UTR）的3'端和整个外显子1（c.-86_c.82）缺失，这可能导致RAD51D蛋白的缺失。RAD51D基因c.82G>A（p.Val28Met）变异具有临床意义，被分类为可能致病。
结论
我们的结果表明，RAD51D基因c.82G>A（p.Val28Met）变异通过破坏正常的mRNA剪接导致癌症易感性。在一名高级别浆液性输卵管癌患者中鉴定出该变异，提示RAD51D变异可能导致该家族患卵巢癌的易感性。
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