title: Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families.
abstract: BACKGROUND
  Recent data show that mutations in RAD51D have an aetiological role in ovarian carcinoma, yet mutations do not appear to be associated with an increased risk for breast cancer. We studied ovarian and breast cancer families having at least one woman affected by ovarian carcinoma, to assess the importance of RAD51D mutations in such families.
  
  
  METHODS
  The coding region of the RAD51D gene was analysed in 175 BRCA1/2-negative families with family histories of both ovarian and breast cancer ascertained from two Canadian and two Belgian institutions.
  
  
  RESULTS
  We identified one previously reported deleterious mutation, p.Arg186(*) (c.556C>T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186(*) segregated with the disease in the family and two ovarian carcinomas available for analysis showed loss of the wild-type allele, but the novel variants are likely neutral.
  
  
  CONCLUSIONS
  RAD51D should be included in genetic screening of ovarian cancer families that do not have BRCA1/BRCA2 mutations. We show that mutations are more likely to be found in families with two or more ovarian cancers, or in probands with first-degree relatives with ovarian cancer, and we feel testing should be preferentially offered to affected women from such families.
authors.affiliation: Program in Cancer Genetics, Departments of Oncology and Human Genetics, Gerald Bronfman Centre for Clinical Research in Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Osher
authors.forename: K
authors.initials: K
authors.lastname: De Leeneer
authors.forename: G
authors.initials: G
authors.lastname: Michils
authors.forename: N
authors.initials: N
authors.lastname: Hamel
authors.forename: E
authors.initials: E
authors.lastname: Tomiak
authors.forename: B
authors.initials: B
authors.lastname: Poppe
authors.forename: K
authors.initials: K
authors.lastname: Leunen
authors.forename: E
authors.initials: E
authors.lastname: Legius
authors.forename: A
authors.initials: A
authors.lastname: Shuen
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Arseneau
authors.forename: P
authors.initials: P
authors.lastname: Tonin
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: K
authors.initials: K
authors.lastname: Claes
authors.forename: M D
authors.initials: MD
authors.lastname: Tischkowitz
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D012680:Sensitivity and Specificity
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004268:DNA-Binding Proteins; C112629:RAD51D protein, human