Unit of Genetics, Laboratory of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene Algiers, Algeria.
Dis Markers. 2010;28(6):377-84. doi: 10.3233/DMA-2010-0718.
Breast cancer is the leading cause of cancer death in women in Algeria. The contribution of BRCA1 and BRCA2 mutations to hereditary breast/ovarian cancer in Algerian population is largely unknown. Here, we describe analysis of BRCA1 and BRCA2 genes in 86 individuals from 70 families from an Algerian cohort with a personal and family history suggestive of genetic predisposition to breast cancer.
The approach used is based on BRCA1 and BRCA2 mutations screening by High-Resolution Melting (HRM) curve analysis followed by direct sequencing. All samples for which no pathogenic mutation was found were analyzed by MLPA for large deletions or duplications.
Three distinct pathogenic mutations c.83_84delTG, c.181T>G, c.798_799delTT and two large rearrangements involving deletion of exon 2 and exon 8 respectively, were detected in BRCA1 gene. Moreover 17 unclassified variants and polymorphisms were detected in BRCA1 gene (6 described for the first time). Two pathogenic mutations, c.1310_1313delAAGA and c.5722_5723delCT and 40 unclassified variants and polymorphisms (14 never described before) were identified in BRCA2 gene.
For the first time, we used HRM and MLPA to identify BRCA1 and BRCA2 mutations in Algerian patients with a personal and family history suggestive of genetic predisposition to breast cancer. The implications of these new findings in regard to genetic testing and counseling are substantial for the Algerian population.
乳腺癌是阿尔及利亚女性癌症死亡的主要原因。BRCA1 和 BRCA2 突变在阿尔及利亚人群遗传性乳腺癌/卵巢癌中的作用尚不清楚。在此，我们描述了对来自具有遗传易感性乳腺癌家族史的 70 个家族的 86 名个体的 BRCA1 和 BRCA2 基因进行分析。
该方法基于 HRM 曲线分析和直接测序对 BRCA1 和 BRCA2 基因突变进行筛选。对未发现致病性突变的所有样本进行 MLPA 分析，以检测大片段缺失或重复。
在 BRCA1 基因中检测到 3 种不同的致病性突变 c.83_84delTG、c.181T>G、c.798_799delTT 和 2 种涉及分别缺失外显子 2 和外显子 8 的大型重排。此外，在 BRCA1 基因中还检测到 17 种未分类的变异和多态性（6 种为首次描述）。在 BRCA2 基因中检测到 2 种致病性突变 c.1310_1313delAAGA 和 c.5722_5723delCT，以及 40 种未分类的变异和多态性（其中 14 种以前从未描述过）。
我们首次使用 HRM 和 MLPA 鉴定了具有遗传易感性乳腺癌家族史的阿尔及利亚患者的 BRCA1 和 BRCA2 突变。这些新发现对遗传检测和咨询对阿尔及利亚人群的影响意义重大。
