• Ana Blanco, Miguel de la Hoya, Ana Osorio, Orland Diez, María Dolores Miramar, Mar Infante, Cristina Martinez-Bouzas, Asunción Torres, Adriana Lasa, Gemma Llort, Joan Brunet, Begoña Graña, Pedro Perez Segura, María José Garcia, Sara Gutiérrez-Enríquez, Ángel Carracedo, María-Isabel Tejada, Eladio A Velasco, María-Teresa Calvo, Judith Balmaña, Javier Benitez, Trinidad Caldés, and Ana Vega.
• Fundación Pública Galega de Medicina Xenómica-Servicio Galego de Saúde, Grupo de Medicina Xenómica-Universidade de Santiago de Compostela, Spanish Network on Rare Diseases (CIBERER), Instituto de Investigaciones Sanitarias de Santiago, Santiago de Compostela, A Coruña, Spain.
• Plos One. 2013 Jan 1; 8 (7): e67538.

BackgroundThe PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer and 3-4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer.Methods132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification.ResultsTwo PALB2 truncating mutations, the c.1653T>A (p.Tyr551Stop) previously reported, and c.3362del (p.Gly1121ValfsX3) which is a novel frameshift mutation, were identified. Moreover, several PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%.ConclusionsThe prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s) involved in the development of breast/pancreatic cancer families is required.

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