Analysis of PALB2 gene in BRCA1/BRCA2 negative Spanish hereditary breast/ovarian cancer families with pancreatic cancer cases

PLoS One. 2013 Jul 23;8(7):e67538. doi: 10.1371/journal.pone.0067538. Print 2013.


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.

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.

Results: 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%.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / complications
  • Breast Neoplasms / congenital*
  • Breast Neoplasms / genetics
  • Computational Biology
  • DNA Mutational Analysis
  • Family
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Humans
  • Male
  • Mutation / genetics
  • Nuclear Proteins / genetics*
  • Ovarian Neoplasms / genetics
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / genetics*
  • Pedigree
  • Spain
  • Tumor Suppressor Proteins / genetics*


  • BRCA1 Protein
  • BRCA2 Protein
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins

Supplementary concepts

  • Breast Cancer, Familial

Grants and funding

This research was supported by grants from the Xunta de Galicia (10PXIB 9101297PR) and FMM Foundation given to AV. MH was supported from the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS) Research Grant 09/00859, and Fundación Mutua Madrileña (FMM) Research Grant FMM-08. SGE is supported by a Miguel Servet contract of the Instituto de Salud Carlos III. EAV was supported in part by grants BIO39/VA27/10 (Consejería de Sanidad) and CSI004A10-2 (Consejería de Educación) from the Junta de Castilla y León. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.