title: Significant contribution of germline BRCA2 rearrangements in male breast cancer families.
abstract: Although screening for large deletions or duplications of the BRCA1 gene is becoming a routine component of the molecular diagnosis of familial breast cancer, little is known about the occurrence of such rearrangements in the BRCA2 gene. Because of the high frequency of BRCA2 mutations in breast cancer families with at least one case of male breast cancer, we selected a cohort of 39 such families, tested negative for mutations in the coding regions of BRCA1 and BRCA2, and developed an assay for BRCA2 rearrangements, based on quantitative multiplex PCR of short fluorescent fragments (QMPSF). We found three rearrangements: (1) a deletion of exons 12 and 13; (2) a duplication of exons 1 and 2; and (3) a complete deletion of BRCA2. We determined the boundaries of the deletion of exons 12 and 13, showing that it resulted from an unequal recombination between Alu sequences. We mapped the complete BRCA2 deletion, which extends over at least 298 kb and showed that it does not affect APRIN/AS3, previously characterized as a tumor suppressor gene, but it comprises several loci corresponding to proven or putative transcripts of unknown functional significance. These data suggest that screening for BRCA2 rearrangements should be done, especially in male breast cancer families tested negative for BRCA1 and BRCA2 mutations.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U614, Faculty of Medicine, IFRMP, University of Rouen, Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tournier
authors.forename: Brigitte Bressac-de
authors.initials: BB
authors.lastname: Paillerets
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Michel
authors.initials: M
authors.lastname: Barrois
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Agnès
authors.initials: A
authors.lastname: Hardouin
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Pierre
authors.initials: P
authors.lastname: Chappuis
authors.forename: Violaine
authors.initials: V
authors.lastname: Bourdon
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.forename: Christine
authors.initials: C
authors.lastname: Maugard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Mario
authors.initials: M
authors.lastname: Tosi
mesh_terms: D018567:Breast Neoplasms, Male / Q000235:genetics*; D015321:Gene Rearrangement; D024522:Genes, BRCA2; D006801:Humans; D008297:Male; D009154:Mutation