title: BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.
abstract: BACKGROUND
  The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC).
  
  
  METHODS
  Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes.
  
  
  RESULTS
  Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P <0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC.
  
  
  CONCLUSIONS
  Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.
authors.affiliation: Institute of Molecular Genetics, Consiglio Nazionale Ricerche, Alghero, Italy. gpalmieri@yahoo.com
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
authors.forename: G
authors.initials: G
authors.lastname: Palomba
authors.forename: A
authors.initials: A
authors.lastname: Cossu
authors.forename: M
authors.initials: M
authors.lastname: Pisano
authors.forename: M F
authors.initials: MF
authors.lastname: Dedola
authors.forename: M G
authors.initials: MG
authors.lastname: Sarobba
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: N
authors.initials: N
authors.lastname: Olmeo
authors.forename: A
authors.initials: A
authors.lastname: Contu
authors.forename: A
authors.initials: A
authors.lastname: Pasca
authors.forename: M P
authors.initials: MP
authors.lastname: Satta
authors.forename: I
authors.initials: I
authors.lastname: Persico
authors.forename: A A
authors.initials: AA
authors.lastname: Carboni
authors.forename: P
authors.initials: P
authors.lastname: Cossu-Rocca
authors.forename: M
authors.initials: M
authors.lastname: Contini
authors.forename: J
authors.initials: J
authors.lastname: Mangion
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
authors.forename: F
authors.initials: F
authors.lastname: Tanda
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling / Q000592:standards* / Q000639:trends; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011159:Population Surveillance; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor