title: Germline 657del5 mutation in the NBS1 gene in breast cancer patients.
abstract: 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.
authors.affiliation: Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin 70-111, Al. Powst. Wlkp. 72, Poland. gorskib@sci.pam.szczecin.pl
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Masojć
authors.forename: Marek
authors.initials: M
authors.lastname: Mierzejewski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Medrek
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Maria
authors.initials: M
authors.lastname: Chosia
authors.forename: Rodney
authors.initials: R
authors.lastname: Scott
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000473:pathology; D016133:Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; C112156:NBN protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins