Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families

Nat Genet. 1996 May;13(1):120-2. doi: 10.1038/ng0596-120.


The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Amino Acid Sequence
  • BRCA1 Protein
  • BRCA2 Protein
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms, Male / genetics*
  • Canada
  • Codon
  • DNA Mutational Analysis
  • Exons
  • Family
  • Female
  • France / ethnology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Pancreatic Neoplasms / genetics
  • Pedigree
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Sequence Deletion*
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • BRCA2 Protein
  • Codon
  • Neoplasm Proteins
  • Transcription Factors