Palomba, Grazia and Cossu, Antonio and Friedman, Eitan and Budroni, Mario and Farris, Antonio and Contu, Antonio and Pisano, Marina and Baldinu, Paola and Sini, Maria Cristina and Tanda, Francesco and Palmieri, Giuseppe (2007) Origin and distribution of the BRCA2-8765delAG mutation in breast cancer. BMC Cancer, Vol. 7 (132), p. 1-7. ISSN 1471-2407. Article.
Background: The BRCA2-8765delAG mutation was firstly described in breast cancer families from French-Canadian and Jewish-Yemenite populations; it was then reported as a founder mutation in Sardinian families. We evaluated both the prevalence of the BRCA2-8765delAG variant in Sardinia and the putative existence of a common ancestral origin through a haplotype analysis of breast cancer family members carrying such a mutation. Methods: Eight polymorphic microsatellite markers (D13S1250, centromeric, to D13S267, telomeric) spanning the BRCA2 gene locus were used for the haplotype analysis. Screening for the 8765delAG mutation was performed by PCR-based amplification of BRCA2-exon 20, followed by automated sequencing. Results: Among families with high recurrence of breast cancer (≥ 3 cases in first-degree relatives), those from North Sardinia shared the same haplotype whereas the families from French Canadian and Jewish-Yemenite populations presented distinct genetic assets at the BRCA2 locus. Screening for the BRCA2-8765delAG variant among unselected and consecutively-collected breast cancer patients originating from the entire Sardinia revealed that such a mutation is present in the northern part of the island only [9/648 (1.4%) among cases from North Sardinia versus 0/493 among cases from South Sardinia]. Conclusion: The BRCA2-8765delAG has an independent origin in geographically and ethnically distinct populations, acting as a founder mutation in North but not in South Sardinia. Since BRCA2- 8765delAG occurs within a triplet repeat sequence of AGAGAG, our study further confirmed the existence of a mutational hot-spot at this genomic position (additional genetic factors within each single population might be involved in generating such a mutation).
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