title: Origin and distribution of the BRCA2-8765delAG mutation in breast cancer.
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 (> or = 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].
  
  
  CONCLUSIONS
  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).
authors.affiliation: Istituto di Chimica Biomolecolare-Consiglio Nazionale Ricerche, Sassari, Italy. graziap68@yahoo.it <graziap68@yahoo.it>
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Antonio
authors.initials: A
authors.lastname: Contu
authors.forename: Marina
authors.initials: M
authors.lastname: Pisano
authors.forename: Paola
authors.initials: P
authors.lastname: Baldinu
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sini
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D002170:Canada / Q000208:ethnology; D005006:Ethnicity; D005260:Female; D005602:France / Q000208:ethnology; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D007557:Israel / Q000208:ethnology; D007558:Italy / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D010375:Pedigree; D018911:Trinucleotide Repeats; D015006:Yemen / Q000208:ethnology
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human