Abstract.Background: 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. Methods: 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. Results: 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. Conclusions: 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.

For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.

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