Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations

Genes Chromosomes Cancer. 2002 Mar;33(3):235-42. doi: 10.1002/gcc.1223.


BARD1 (BRCA1-associated RING domain) was identified by yeast two-hybrid screening as a protein interacting with BRCA1. Somatic and germline mutations of BARD1 have been detected in sporadic breast, ovarian, and endometrial cancers. The present study represents the first description of BARD1 germline mutations in hereditary breast and breast/ovarian cancer patients. We analyzed the BARD1 gene in 40 families with hereditary breast and breast/ovarian cancer, tested negative for BRCA1 and BRCA2 mutations. A mutational analysis by PCR-SSCP on the coding region and the exon-intron splice boundaries of the BARD1 gene yielded four different germline mutations. A group of 20 patients diagnosed with sporadic breast cancer below the age of 40 was also examined and only one germline mutation was found. A study of loss of heterozygosity at the BARD1 locus in neoplastic tissues from patients with BARD1 germline mutations was carried out. In all cases, we were unable to find any evidence for allelic deletions. The involvement of BARD1 mutations in the susceptibility to hereditary breast and breast/ovarian cancer is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics
  • Carrier Proteins / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Germ-Line Mutation / genetics*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Protein Structure, Tertiary / genetics
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*


  • BRCA1 Protein
  • Carrier Proteins
  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases