title: The contribution of germline rearrangements to the spectrum of BRCA2 mutations.
abstract: BACKGROUND
  Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer.
  
  
  OBJECTIVE
  To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects.
  
  
  METHODS
  Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2.
  
  
  RESULTS
  We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum.
  
  
  CONCLUSIONS
  The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.
authors.affiliation: Inserm U614, IFRMP, Faculty of Medicine, Rouen, France.
authors.forename: F
authors.initials: F
authors.lastname: Casilli
authors.forename: I
authors.initials: I
authors.lastname: Tournier
authors.forename: O M
authors.initials: OM
authors.lastname: Sinilnikova
authors.forename: F
authors.initials: F
authors.lastname: Coulet
authors.forename: F
authors.initials: F
authors.lastname: Soubrier
authors.forename: C
authors.initials: C
authors.lastname: Houdayer
authors.forename: A
authors.initials: A
authors.lastname: Hardouin
authors.forename: P
authors.initials: P
authors.lastname: Berthet
authors.forename: H
authors.initials: H
authors.lastname: Sobol
authors.forename: V
authors.initials: V
authors.lastname: Bourdon
authors.forename: D
authors.initials: D
authors.lastname: Muller
authors.forename: J P
authors.initials: JP
authors.lastname: Fricker
authors.forename: C
authors.initials: C
authors.lastname: Capoulade-Metay
authors.forename: A
authors.initials: A
authors.lastname: Chompret
authors.forename: C
authors.initials: C
authors.lastname: Nogues
authors.forename: S
authors.initials: S
authors.lastname: Mazoyer
authors.forename: P
authors.initials: P
authors.lastname: Chappuis
authors.forename: P
authors.initials: P
authors.lastname: Maillet
authors.forename: C
authors.initials: C
authors.lastname: Philippe
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.forename: P
authors.initials: P
authors.lastname: Gesta
authors.forename: S
authors.initials: S
authors.lastname: Bézieau
authors.forename: C
authors.initials: C
authors.lastname: Toulas
authors.forename: L
authors.initials: L
authors.lastname: Gladieff
authors.forename: C M
authors.initials: CM
authors.lastname: Maugard
authors.forename: D M
authors.initials: DM
authors.lastname: Provencher
authors.forename: C
authors.initials: C
authors.lastname: Dugast
authors.forename: C
authors.initials: C
authors.lastname: Delvincourt
authors.forename: T D
authors.initials: TD
authors.lastname: Nguyen
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: V
authors.initials: V
authors.lastname: Bonadona
authors.forename: T
authors.initials: T
authors.lastname: Frébourg
authors.forename: R
authors.initials: R
authors.lastname: Lidereau
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: M
authors.initials: M
authors.lastname: Tosi
mesh_terms: D005091:Exons / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics