title: Identification of a founder BRCA2 mutation in Sardinia.
abstract: Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12-q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a 'frame-shift' mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours.
authors.affiliation: Istituto di Genetica Molecolare, CNR, Sassari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pisano
authors.forename: A
authors.initials: A
authors.lastname: Cossu
authors.forename: I
authors.initials: I
authors.lastname: Persico
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
authors.forename: A
authors.initials: A
authors.lastname: Angius
authors.forename: G
authors.initials: G
authors.lastname: Casu
authors.forename: G
authors.initials: G
authors.lastname: Palomba
authors.forename: M G
authors.initials: MG
authors.lastname: Sarobba
authors.forename: P C
authors.initials: PC
authors.lastname: Rocca
authors.forename: M F
authors.initials: MF
authors.lastname: Dedola
authors.forename: N
authors.initials: N
authors.lastname: Olmeo
authors.forename: A
authors.initials: A
authors.lastname: Pasca
authors.forename: M
authors.initials: M
authors.lastname: Budroni
authors.forename: V
authors.initials: V
authors.lastname: Marras
authors.forename: A
authors.initials: A
authors.lastname: Pisano
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: G
authors.initials: G
authors.lastname: Massarelli
authors.forename: M
authors.initials: M
authors.lastname: Pirastu
authors.forename: F
authors.initials: F
authors.lastname: Tanda
mesh_terms: D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D018703:Founder Effect; D006801:Humans; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D017931:DNA Primers; D009363:Neoplasm Proteins; D014157:Transcription Factors