title: Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations.
abstract: BRCA1 and BRCA2 are the two major genes predisposing to breast and ovarian cancer. Whereas high de novo mutation rates have been demonstrated for several genes, only 11 cases of de novo BRCA1/2 mutations have been reported to date and the BRCA1/2 de novo mutation rate remains unknown. The present study was designed to fill this gap based on a series of 12 805 consecutive unrelated patients diagnosed with breast and/or ovarian cancer who met the inclusion criteria for BRCA1/2 gene analysis according to French guidelines. BRCA1/2 mutations were detected in 1527 (12%) patients, and three BRCA1 mutations and one BRCA2 mutation were de novo. The BRCA1/2 de novo mutation rate was estimated to be 0.3% (0.1%; 0.7%). Although rare, it may be useful to take the possibility of de novo BRCA1/2 mutation into account in genetic counseling of relatives and to improve the understanding of complex family histories of breast and ovarian cancers.
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.|Institut Curie, Inserm U830, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Golmard
authors.affiliation: CHU Nantes, Service de Génétique médicale, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Delnatte
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Laugé
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Moncoutier
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lefol
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Abidallah
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Tenreiro
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Copigny
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Giraudeau
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Guy
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Barbaroux
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Amorim
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Briaux
authors.affiliation: CHU Nantes, Service de Génétique médicale, Nantes, France.
authors.forename: V
authors.initials: V
authors.lastname: Guibert
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.|Institut Curie, Inserm U830, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Tarabeux
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Caputo
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Collet
authors.affiliation: Pôle Oncologie, Oncogénétique Poitou-Charentes, Niort, France.
authors.forename: P
authors.initials: P
authors.lastname: Gesta
authors.affiliation: CHU Angers, Service de Génétique médicale, Angers, France.
authors.forename: O
authors.initials: O
authors.lastname: Ingster
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.|Institut Curie, Inserm U830, Paris, France.
authors.forename: M-H
authors.initials: MH
authors.lastname: Stern
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: de Pauw
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Gauthier-Villars
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Buecher
authors.affiliation: CHU Nantes, Service de Génétique médicale, Nantes, France.|Université de Nantes, Faculté de Médecine de Nantes, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Bézieau
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.|Institut Curie, Inserm U830, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.affiliation: Institut Curie, Département de Biopathologie, Paris, France.|Institut Curie, Inserm U830, Paris, France.|Faculté des Sciences pharmaceutiques et biologiques, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Houdayer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*