title: Germline 657del5 mutation in the NBS1 gene in patients with malignant melanoma of the skin.
abstract: In this study we determined in what proportion of consecutive malignant melanoma (MM) cases the 657del5 mutation of exon 6 of the NBS1 gene can be detected and whether it is associated with the occurrence of MM. Two groups of patients were studied: a series of 80 consecutive patients with histologically confirmed MM of the skin diagnosed in the city of Szczecin, Poland, and a series of 530 consecutive individuals selected at random by family doctors from the city of Szczecin. Molecular examination included an allele-specific polymerase chain reaction assay for the NBS1 founder mutation (657del5), genomic sequencing, loss of heterozygosity analysis using CA-repeat microsatellite markers, and haplotype analysis. The NBS1 founder mutation was detected in two of the 80 (2.5%) MM cases and in three of the 530 individuals (0.6%) from the general population. The difference was not statistically significant. However, examination of tumorous DNA from the patients with MM and NBS1 mutation revealed loss of heterozygosity in both cases. Haplotype analysis revealed that allellic loss affects wild-type alleles. Breast cancer was found in second-degree relatives of both MM probands with NBS1 mutations. One of these probands was simultaneously affected with breast cancer. It seems that the 657del5 mutation of exon 6 of NBS1 gene may be responsible for the occurrence of a small proportion of MM patients, characterized by the occurrence of breast cancer among their relatives.
authors.affiliation: Department of Genetics, Pomeranian Academy of Medicine, Szczecin 70-111, Poland. debniak@wp.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
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: Marcin
authors.initials: M
authors.lastname: Lener
authors.forename: Marek
authors.initials: M
authors.lastname: Mierzejewski
authors.forename: Bartosz
authors.initials: B
authors.lastname: Masojć
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Medrek
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Załuga
authors.forename: Romuald
authors.initials: R
authors.lastname: Maleszka
authors.forename: Maria
authors.initials: M
authors.lastname: Chosia
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D015897:Comorbidity; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005828:Genetics, Population; D018095:Germ-Line Mutation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D011044:Poland / Q000453:epidemiology; D015995:Prevalence; D011897:Random Allocation; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C112156:NBN protein, human; D009687:Nuclear Proteins