Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer

Breast Cancer Res Treat. 2012 Feb;132(1):307-15. doi: 10.1007/s10549-011-1842-2. Epub 2011 Nov 4.


It has been demonstrated that monoallelic PALB2 (Partner and Localizer of BRCA2) gene mutations predispose to familial breast cancer. Some of the families reported with germline PALB2 mutations presented male breast cancer as a characteristic clinical feature. Therefore, we wanted to investigate the contribution of germline PALB2 mutations in a set of 131 Spanish BRCA1/BRCA2-negative breast/ovarian cancer families with at least one male breast cancer case. The analysis included direct sequencing of all coding exons and intron/exon boundaries as well as a Multiplex Ligation-dependent Probe Amplification-based analysis of genomic rearrangements. For the first time we have identified a genomic rearrangement of PALB2 gene involving a large deletion from exon 7 to 11 in a breast cancer family. We have also identified several PALB2 variants, but no other obvious deleterious PALB2 mutation has been found. Thus, our study does not support an enrichment of PALB2 germline mutations in the subset of breast cancer families with male breast cancer cases. The identification of intronic and exonic variants indicates the necessity of assessing the implications of variants that do not lead to PALB2 truncation in the pathoghenicity of the PALB2 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms, Male / genetics*
  • Exons
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genetic Association Studies
  • Genetic Carrier Screening
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Pedigree
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Spain
  • Tumor Suppressor Proteins / genetics*


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