Genetic and Cancer Medical Laboratory HCL-CLB, Hospices Civils de Lyon, 69008 Lyon, France.
Institute for Advanced Biosciences, University Grenoble Alpes, INSERM, CNRS, 38000 Grenoble, France.
Int J Mol Sci. 2022 Jan 8;23(2):667. doi: 10.3390/ijms23020667.
(partner and localizer of ), as indicated by its name, is a -interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in , implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of variants and may improve the yield of genetic diagnoses in this field.
作为一个与 相互作用的蛋白，如其名所示，在同源重组（HR）和 DNA 双链断裂（DSB）修复中起着重要作用。虽然 中的致病变异已被充分证明会增加乳腺癌的风险，但它在前列腺癌（PrC）中的作用的数据尚未得到明确证实。我们使用靶向下一代测序（NGS）研究了一名 59 岁的白种人，他同时患有乳腺癌和前列腺癌。这项遗传研究发现了 基因内的种系杂合性重复，涉及跨越第 11 外显子的内含子重复序列。该变体通过多重连接探针扩增（MLPA）得到证实，并使用基于步行 PCR、长距离 PCR 和 Sanger 测序的方法在核苷酸水平上鉴定和表征了基因组断点（c.3114-811_3202-1756dup）。使用从淋巴细胞中提取的 mRNA 进行 RT-PCR，然后进行 Sanger 测序，发现串联重复 r.3114_3201dup;p.（Gly1068Glufs * 14）。这种重复导致截短的、极有可能无功能的蛋白的合成。这些发现扩展了 变异的表型谱，并可能提高该领域遗传诊断的产量。
