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

作者：Blanco Ana; de la Hoya Miguel; Osorio Ana; Diez Orland; Dolores Miramar Maria; Infante Mar; Martinez Bouzas Cristina; Torres Asuncion; Lasa Adriana; Llort Gemma; Brunet Joan; Grana Begona; Perez Segura Pedro; Jose Garcia Maria; Gutierrez Enriquez Sara; Carracedo Angel; Tejada Maria Isabel; Velasco Eladio A; Calvo Maria Teresa; Balmana Judith; Benitez Javier; Caldes Trinidad; Vega Ana^*

来源：PLos One, 2013, 8(7): e67538.

DOI：10.1371/journal.pone.0067538

Background: 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. %26lt;br%26gt;Methods: 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. %26lt;br%26gt;Results: Two PALB2 truncating mutations, the c.1653T%26gt;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%. %26lt;br%26gt;Conclusions: 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.

• 出版日期2013-7-23