Journal Article

Analysis of PALB2 Gene in BRCA1/BRCA2 Negative Spanish Hereditary Breast/Ovarian Cancer Families with Pancreatic Cancer Cases

Vega, Ana, Osorio, Ana, Perez Segura, Pedro, Llort, Gemma, Diez, Orland, Caldés, Trinidad, Infante, Mar, Torres, Asunción, Blanco, Ana, Miramar, María Dolores, Graña, Begoña, de la Hoya, Miguel, Gutiérrez-Enríquez, Sara, Benitez, Javier, Martinez-Bouzas, Cristina, Balmaña, Judith, Carracedo, Ángel, Garcia, María José, Calvo, María-Teresa, Lasa, Adriana, Tejada, María-Isabel, Velasco, Eladio A., Brunet, Joan

2013

Overview

The 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. 132 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. Two 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%. The 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology / BRCA1 protein / BRCA1 Protein - genetics / BRCA2 protein / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms - complications / Breast Neoplasms - congenital / Breast Neoplasms - genetics / Cancer / Cancer genetics / Cancer research / Computational Biology / Deoxyribonucleic acid / Development and progression / DNA / DNA Mutational Analysis / DNA repair / Exons / Family / Fanconi Anemia Complementation Group N Protein / Female / Frameshift mutation / Gene mutation / Genes / Genetic aspects / Genetics / Health risk assessment / Humans / Male / Medical diagnosis / Medicine / Multiplexing / Mutation / Mutation - genetics / Nuclear Proteins - genetics / Ovarian cancer / Ovarian carcinoma / Ovarian Neoplasms - genetics / Pancreatic cancer / Pancreatic Neoplasms - complications / Pancreatic Neoplasms - genetics / Patients / Pedigree / Spain / Tumor Suppressor Proteins - genetics