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).

Origin and distribution of the BRCA2-8765delAG mutation in breast cancer / Palomba, Grazia; Cossu, Antonio; Friedman, Eitan; Budroni, Mario; Farris, Antonio; Contu, Antonio; Pisano, Marina; Baldinu, Paola; Sini Maria, C.; Tanda, Francesco; Palmieri, Giuseppe. - In: BMC CANCER. - ISSN 1471-2407. - 7:(2007). [10.1186/1471-2407-7-132]

Origin and distribution of the BRCA2-8765delAG mutation in breast cancer

Cossu Antonio;TANDA, Francesco;Palmieri Giuseppe
Investigation
2007-01-01

Abstract

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).
2007
Origin and distribution of the BRCA2-8765delAG mutation in breast cancer / Palomba, Grazia; Cossu, Antonio; Friedman, Eitan; Budroni, Mario; Farris, Antonio; Contu, Antonio; Pisano, Marina; Baldinu, Paola; Sini Maria, C.; Tanda, Francesco; Palmieri, Giuseppe. - In: BMC CANCER. - ISSN 1471-2407. - 7:(2007). [10.1186/1471-2407-7-132]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/61809
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 11
social impact