title: Mutation analysis of PALB2 gene in French breast cancer families.
abstract: Several population-based and family-based studies have demonstrated that germline mutations of the PALB2 gene (Partner and Localizer of BRCA2) are associated with an increased risk of breast cancer. Distinct mutation frequencies and spectrums have been described depending on the population studied. Here we describe the first complete PALB2 coding sequence screening in the French population. We screened the complete coding sequence and intron-exon boundaries of PALB2, using the EMMA technique, to assess the contribution of pathogenic mutations in a set of 835 familial breast cancer cases and 662 unrelated controls from the French national study GENESIS and the Paul Strauss Cancer Centre, all previously tested negative for BRCA1 and BRCA2 pathogenic mutations. Our analysis revealed the presence of four novel deleterious mutations: c.1186insT, c.1857delT and c.2850delC in three cases, c.3418dupT in one control. In addition, we identified two in-frame insertion/deletion, 19 missense substitutions (two of them predicted as pathogenic), 9 synonymous variants, 28 variants located in introns and 2 in UTRs, as well as frequent variants. Truncating PALB2 mutations were found in 0.36% of familial breast cancer cases, a frequency lower than the one detected in comparable studies in other populations (0.73-3.40%). This suggests a small but significant contribution of PALB2 mutations to the breast cancer susceptibility in the French population.
authors.affiliation: "Genetics of Breast Cancer" Team, Cancer Research Centre of Lyon, CNRS UMR5286/Inserm U1052/Université Lyon 1, Centre Léon Bérard, Lyon, France. francesca.damiola@lyon.unicancer.fr.
authors.forename: Francesca
authors.initials: F
authors.lastname: Damiola
authors.affiliation: Unité d'Oncologie Génétique, Centre Paul Strauss, Strasbourg, France.
authors.forename: Inès
authors.initials: I
authors.lastname: Schultz
authors.affiliation: "Genetics of Breast Cancer" Team, Cancer Research Centre of Lyon, CNRS UMR5286/Inserm U1052/Université Lyon 1, Centre Léon Bérard, Lyon, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Barjhoux
authors.affiliation: "Genetics of Breast Cancer" Team, Cancer Research Centre of Lyon, CNRS UMR5286/Inserm U1052/Université Lyon 1, Centre Léon Bérard, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sornin
authors.affiliation: INSERM, U900, Paris, France.|Institut Curie, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Marie-Gabrielle
authors.initials: MG
authors.lastname: Dondon
authors.affiliation: INSERM, U900, Paris, France.|Institut Curie, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Eon-Marchais
authors.affiliation: INSERM, U900, Paris, France.|Institut Curie, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Marcou
authors.affiliation: Service d'Oncologie Génétique, Institut de Cancérologie Gustave Roussy, Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: de Pauw
authors.affiliation: Unité d'Oncogénétique, ICL Alexis Vautrin, Vandœuvre-lès-Nancy, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.affiliation: Unité de Pathologie Gynécologique, Centre François Baclesse, Caen, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.affiliation: Service Oncologie Médicale, Centre René Gauducheau, Nantes Saint Herblain, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Delnatte
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France.|CNRS UMR 5558, Lyon, France.|Unité de Prévention et Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.affiliation: Service d'Oncologie, UF6948, Hôpital Civil, Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Maugard
authors.affiliation: Service de Génétique Médicale et Oncogénétique, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France.|INSERM U896, CRCM Val d'Aurel, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France.|CNRS UMR 5558, Lyon, France.|Unité de Prévention et Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.affiliation: Centre Jean-Perrin, Clermont-Ferrand, France.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Unité d'Oncologie Génétique, Centre Paul Strauss, Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.affiliation: INSERM, U900, Paris, France.|Institut Curie, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.affiliation: "Genetics of Breast Cancer" Team, Cancer Research Centre of Lyon, CNRS UMR5286/Inserm U1052/Université Lyon 1, Centre Léon Bérard, Lyon, France.|Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.affiliation: Service de Génétique, Institut Curie, Paris, France.|Inserm, U830, Paris, France.|Université Paris-Descartes, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.affiliation: "Genetics of Breast Cancer" Team, Cancer Research Centre of Lyon, CNRS UMR5286/Inserm U1052/Université Lyon 1, Centre Léon Bérard, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.affiliation: Unité d'Oncologie Génétique, Centre Paul Strauss, Strasbourg, France. dmuller@strasbourg.unicancer.fr.
authors.forename: Danièle
authors.initials: D
authors.lastname: Muller
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
keywords: Familial breast cancer; Genetic testing; Germline mutations; PALB2