Germline 657del5 mutation in the NBS1 gene in breast cancer patients

Int J Cancer. 2003 Sep 1;106(3):379-81. doi: 10.1002/ijc.11231.


In this report the proportion of consecutive and familial breast cancer cases harboring the 657del5 of exon 6 of the NBS1 gene was determined to assess whether it is associated with the increased risk of breast cancer development. The study consisted of 3 groups of patients: a series of consecutive 150 patients with histologically confirmed breast cancer, diagnosed under the age of 50 in the city of Szczecin; a series of 80 breast cancer patients with a family history of breast cancer in their first-degree relatives; and a series of 530 consecutive individuals without the diagnosis of breast cancer selected at random by family doctors from the city of Szczecin. Molecular examination included allele-specific PCR assay for the common Slavic NBS1 mutation (657del5), LOH analysis using denucleotide CA repeat microsatellite markers, haplotype analysis and sequencing. The NBS1 founder mutation was detected in 2 of 150 (1.3%) consecutive breast cancer cases diagnosed under the age of 50 years; in 3 of 80 familial breast cancer cases (3.7%); and in 3 of 530 individuals (0.6%) from the general population. Examination of tumor DNA from patients with the NBS1 mutation (groups A and B) revealed loss of heterozygosity (LOH) in all cases. Additional haplotype analysis revealed that allelic loss affects specifically wild-type alleles. The majority of probands with breast cancer and the NBS1 mutation had a positive family history of breast cancer in their first-degree relatives. It appears that the 657del5 mutation in exon 6 of the NBS1 gene is responsible for the occurrence of a small but significant proportion of familial breast cancer patients.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Exons
  • Female
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Haplotypes
  • Humans
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / pathology
  • Polymerase Chain Reaction


  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DNA Primers
  • DNA, Neoplasm
  • NBN protein, human
  • Neoplasm Proteins
  • Nuclear Proteins