Complete mutation screening and haplotype characterization of BRCA1 gene in Tunisian patients with familial breast cancer.

Breast cancer, the most commonly diagnosed cancer in women, is the second leading cause of cancer death in women worldwide. To investigate the contribution of BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of all BRCA1 exons. We identified four different BRCA1 frameshift mutations: c.4041delAG, c.2551delG and c.5266dupC already been described and one novel mutation, c.211dupA, observed in two unrelated families. C.5266dupC has previously been found among Jewish Ashkenazi and Eastern European populations. Our study describes it in Arabic/Berber population. Five out of thirty two familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study is the first molecular investigation on the role of BRCA1 in hereditary breast cancer in North Tunisia.

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia.

Hereditary breast cancer accounts for 3-8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations--c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.