title: BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.
abstract: OBJECTIVE
  To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile.
  
  
  METHODS
  A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total of 106 unrelated families affected with breast and/or ovarian cancer screened for mutations occurring in the whole BRCA1 gene by automatic direct sequencing.
  
  
  RESULTS
  Germline BRCA1 mutations were found in 17 of 106 (16%) Sicilian families. The HBOC profile had a major frequency (66%) of mutations (P < 0.01). A total of 28 sequence variants was identified. Seven of these were pathogenic, 5 unknown biological variant (UV) and 16 polymorphisms. We also identified a pathological mutation (4843delC) as a possible Sicilian founder mutation.
  
  
  CONCLUSIONS
  The present study is the first BRCA1 disease-associated mutations analysis in Southern Italian families. The early age of onset of such tumors and the association with the HBOC familial profile could be two valid screening factors for the identification of BRCA1 mutation carriers. Finally, we identified a BRCA1 mutation with a possible founder effect.
authors.affiliation: Interdepartmental Center of Clinical Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, Università di Palermo, Via del Vespro 127, 90127, Palermo, Italy. lab-oncobiologia@usa.net
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Valentina
authors.initials: V
authors.lastname: Calò
authors.forename: Valentina
authors.initials: V
authors.lastname: Agnese
authors.forename: Loredana
authors.initials: L
authors.lastname: Bruno
authors.forename: Simona
authors.initials: S
authors.lastname: Corsale
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.forename: Grazia
authors.initials: G
authors.lastname: Gargano
authors.forename: Floriana
authors.initials: F
authors.lastname: Barbera
authors.forename: Sandra
authors.initials: S
authors.lastname: Cascio
authors.forename: Chiara
authors.initials: C
authors.lastname: Intrivici
authors.forename: Gaetana
authors.initials: G
authors.lastname: Rinaldi
authors.forename: Gaspare
authors.initials: G
authors.lastname: Gulotta
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Eva
authors.initials: E
authors.lastname: Surmacz
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D019313:BRCA1 Protein