Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115, Szczecin, Poland,
Mol Biol Rep. 2013 Dec;40(12):6619-23. doi: 10.1007/s11033-013-2775-0. Epub 2013 Sep 25.
BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility. In Poland standard BRCA gene test is usually limited to Polish founder BRCA1 mutations: 5382insC, C61G and 4153delA. To date, just a few single large genomic rearrangements (LGRs) of BRCA1 gene have been reported in Poland. Here we report the first comprehensive analysis of large mutations in BRCA1 and BRCA2 genes in this country. We screened LGRs in BRCA1 and BRCA2 genes by multiplex ligation-dependent probe amplification in 200 unrelated patients with strong family history of breast/ovarian cancers and negative for BRCA1 Polish founder mutations. We identified three different LGRs in BRCA1 gene: exons 13-19 deletion, exon 17 deletion and exon 22 deletion. No LGR was detected in BRCA2 genes. Overall, large rearrangements accounted for 3.7 % of all BRCA1 mutation positive families in our population and 1.5 % in high-risk families negative for Polish founder mutation.
BRCA1 和 BRCA2 是与家族性乳腺癌和卵巢癌易感性相关的两个主要基因。在波兰，标准的 BRCA 基因检测通常仅限于波兰的 BRCA1 基因突变：5382insC、C61G 和 4153delA。迄今为止，波兰只报道了少数几种 BRCA1 基因的大型基因组重排（LGRs）。在这里，我们报告了在波兰首次对 BRCA1 和 BRCA2 基因中的大型突变进行的全面分析。我们通过多重连接依赖性探针扩增，对 200 名具有强烈乳腺癌/卵巢癌家族史且 BRCA1 波兰创始人突变阴性的无关患者进行了 LGRs 筛查。我们在 BRCA1 基因中发现了三种不同的 LGR：外显子 13-19 缺失、外显子 17 缺失和外显子 22 缺失。BRCA2 基因中未检测到 LGR。总体而言，大型重排占我们人群中所有 BRCA1 突变阳性家族的 3.7%，在波兰创始人突变阴性的高危家族中占 1.5%。
