种系 DNA 修复基因在转移性去势抵抗性前列腺癌患者中的突变。
Germline Mutations in DNA Repair Genes in Patients With Metastatic Castration-resistant Prostate Cancer.
机构信息
Department of Urology, Jessenius Faculty of Medicine in Martin and University Hospital Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
出版信息
In Vivo. 2020 Jul-Aug;34(4):1773-1778. doi: 10.21873/invivo.11971.
BACKGROUND/AIM: The aim of this study was to analyse the genetic profiles of metastatic castration-resistant prostate cancer (mCRPC) by using next generation sequencing to identify variants with pathogenic potential in nine DNA repair genes - BRCA1, BRCA2, RAD50, RAD51, RAD51C/D, ATM and ATR.
MATERIALS AND METHODS
Isolated genomic DNA from peripheral blood of 50 patients with mCRPC was used for the sequencing of 111 genes associated with hereditary cancer on an Illumina platform. Identified variants were tested in Integrative Genomic Viewer, their clinical significance confirmed in databases and their potential impact on protein function predicted by in silico tools.
RESULTS
From nine analysed DNA repair genes, we identified 14 relevant variants; three pathogenic variants - BRCA2 (rs80359306), RAD50 (rs786201531) and ATM (rs1555099760), and eleven other variants with pathogenic potential.
CONCLUSION
The pathogenic variants identified in this study are located in evolutionarily conserved regions of proteins and are highly likely to affect DNA repair efficiency.
背景/目的：本研究旨在通过下一代测序分析转移性去势抵抗性前列腺癌（mCRPC）的遗传图谱，以鉴定九个 DNA 修复基因（BRCA1、BRCA2、RAD50、RAD51、RAD51C/D、ATM 和 ATR）中具有潜在致病性的变体。
材料和方法
从 50 名 mCRPC 患者的外周血中分离出基因组 DNA，用于在 Illumina 平台上对与遗传性癌症相关的 111 个基因进行测序。在 Integrative Genomic Viewer 中对鉴定出的变体进行检测，在数据库中确认其临床意义，并通过计算机工具预测其对蛋白质功能的潜在影响。
结果
从分析的九个 DNA 修复基因中，我们鉴定出了 14 个相关变体；三个致病性变体——BRCA2（rs80359306）、RAD50（rs786201531）和 ATM（rs1555099760），以及另外 11 个具有潜在致病性的变体。
结论
本研究中鉴定出的致病性变体位于蛋白质的进化保守区域，很可能影响 DNA 修复效率。
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