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Mutation analysis of PALB2 gene in French breast cancer families

By Francesca Damiola, Inès Schultz, Laure Barjhoux, Valérie Sornin, Marie-Gabrielle Dondon, Séverine Eon-Marchais, Morgane Marcou, Olivier Caron, Marion Gauthier-Villars, Antoine De Pauw, Elisabeth Luporsi, Pascal Berthet, Capucine Delnatte, Valérie Bonadona, Christine Maugard, Pascal Pujol, Christine Lasset, Michel Longy, Yves-Jean Bignon, Jean-Pierre Fricker, Nadine Andrieu, Olga Sinilnikova, Dominique Stoppa-Lyonnet, Sylvie Mazoyer and Danièle Muller

Abstract

International audienceSeveral 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

Topics: Familial breast cancer, Genetic testing, Germline mutations, PALB2, [SDV.CAN]Life Sciences [q-bio]/Cancer
Publisher: 'Springer Science and Business Media LLC'
Year: 2015
DOI identifier: 10.1007/s10549-015-3625-7
OAI identifier: oai:HAL:hal-01899538v1
Provided by: HAL-HCL
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