西班牙东南部穆尔西亚地区遗传性乳腺癌和卵巢癌家族中RAD51C和RAD51D基因的突变分析

Mutational analysis of RAD51C and RAD51D genes in hereditary breast and ovarian cancer families from Murcia (southeastern Spain).

作者信息

Sánchez-Bermúdez Ana Isabel, Sarabia-Meseguer Ma Desamparados, García-Aliaga Ángeles, Marín-Vera Miguel, Macías-Cerrolaza José Antonio, Henaréjos Pilar Sánchez, Guardiola-Castillo Verónica, Peña Francisco Ayala-de la, Alonso-Romero José Luis, Noguera-Velasco José Antonio, Ruiz-Espejo Francisco

机构信息

Genetic Diagnostic Laboratory, Department of Clinical Analyses, Virgen de La Arrixaca University Hospital, Spain.

出版信息

Eur J Med Genet. 2018 Jun;61(6):355-361. doi: 10.1016/j.ejmg.2018.01.015. Epub 2018 Feb 2.

DOI:10.1016/j.ejmg.2018.01.015

PMID:29409816

Abstract

RAD51C and RAD51D have been defined as susceptibility genes for hereditary breast and ovarian cancer syndrome in several studies. In the present study, a mutation analysis of these genes was performed on non BRCA1/2 families. RAD51C and RAD51D genes were analyzed in 141 and 77 families, respectively. The analysis included direct sequencing and multiple ligation probe analysis. The RAD51C pathogenic variant c.404G > A was identified in a breast and ovarian cancer family (0.7%), while the RAD51D pathogenic variant c.694C > T was described in an ovarian cancer family (1.3%). Moreover, three unknown clinical significance variants were detected: c.307T > G in RAD51C, and c.413A > G and c.715C > T in RAD51D. No large genomic rearrangements (LGRs) were found. RAD51D carriers suffered from premenopausal ovarian tumors. These results increase our knowledge about the RAD51C and RAD51D mutation spectrum and support the notion that these genes should be included in the gene panel testing performed on patients with hereditary breast and ovarian cancer syndrome.

摘要

在多项研究中，RAD51C和RAD51D已被定义为遗传性乳腺癌和卵巢癌综合征的易感基因。在本研究中，对非BRCA1/2家系进行了这些基因的突变分析。分别对141个和77个家系的RAD51C和RAD51D基因进行了分析。分析包括直接测序和多重连接探针分析。在一个乳腺癌和卵巢癌家系中鉴定出RAD51C致病变异c.404G＞A（0.7%），而在一个卵巢癌家系中描述了RAD51D致病变异c.694C＞T（1.3%）。此外，还检测到三个临床意义不明的变异：RAD51C中的c.307T＞G，以及RAD51D中的c.413A＞G和c.715C＞T。未发现大的基因组重排（LGR）。RAD51D携带者患有绝经前卵巢肿瘤。这些结果增加了我们对RAD51C和RAD51D突变谱的了解，并支持将这些基因纳入对遗传性乳腺癌和卵巢癌综合征患者进行的基因检测面板的观点。