title: Nijmegen breakage syndrome gene (NBS1) alterations and its protein (nibrin) expression in human ovarian tumours.
abstract: We looked for NBS1 gene (602667) alterations and changes in nibrin expression in 162 human gynaecological tumours, mostly ovarian. Exons 6-8 and 10 of the NBS1 gene were evaluated by the SSCP and direct sequencing method. Nibrin expression was detected immunohistochemically with the use of the p95NBS1 (Ab-1) antibody. The 657del5 mutation (Slavic mutation) was found in two of 117 carcinomas studied (1.7%) - in both cases it was present in the germline; one of these tumours showed loss of heterozygosity (LOH) for the 657del5 mutation and loss of nibrin expression. We have found three types of novel germline intron variants: (1) two concomitant transitions (G to A) at bases 14009 and 14256; (2) C to T transition at base 13998; (3) G to C transversion at base 20035. Among the carcinomas studied, the intron variants were associated with a clear cell histological type (p = 0.004). Our results may suggest that NBS1 gene alterations contribute to the development of rare ovarian carcinomas. LOH for 657del5 in tumour tissue may support the hypothesis that the NBS1 gene functions as a tumour suppressor.
authors.affiliation: Department of Molecular Pathology, the Maria Skłodowska-Curie Memorial Cancer Center, Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Plisiecka-Hałasa
authors.forename: A
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.forename: A
authors.initials: A
authors.lastname: Rembiszewska
authors.forename: M
authors.initials: M
authors.lastname: Bidziński
authors.forename: J
authors.initials: J
authors.lastname: Steffen
authors.forename: J
authors.initials: J
authors.lastname: Kupryjańczyk
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000906:Antibodies / Q000378:metabolism; D001483:Base Sequence; D002277:Carcinoma / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D000906:Antibodies; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins