title: The frequency of NBN molecular variants in pediatric astrocytic tumors.
abstract: Gliomas, particularly those of astrocytic origin, are the most frequent primary central nervous system tumors that develop in children. The majority of them are benign and slow growing, with relatively good prognosis. Several genomic and gene alterations are known to be involved in astrocytoma development, but the precise mechanisms remain poorly understood. The NBN gene, which participates in DNA double-strand break repair and maintenance of genome stability, has been postulated to be a susceptibility factor for a number of cancers. Here we report the results of NBN gene analyses performed in 127 children with various astrocytic tumors. PCR-SSCP analysis followed by DNA sequencing was used for molecular variant screening. Three carriers (2.37%) of different germline mutations on one NBN allele were found. The common Slavic deletion c.657_661del5 (p.K219fsX19) was detected in a patient with pilocytic astrocytoma; a known mutation, c.643C>T (p.R215W), and a new substitution, c.565C>G (p.Q189E), were identified in two patients with primary glioblastoma. The risk of developing astrocytic malignancies is estimated to be 1.33 times higher for c.657_661del5 and 3.2 times higher for c.643C>T than in the general Polish population (P > 0.05). Because of the low frequency of the mutations identified in the studied group, we were unable to determine the exact role of NBN in the development of astrocytoma in children. The presence of two potentially pathogenic NBN molecular variants among 16 glioblastoma cases (12.5%) could be a remarkable finding in our study. We thus cannot exclude a possible role of NBN in the tumorigenesis of a certain type of astrocytic tumors.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Ciara
authors.forename: Ewa
authors.initials: E
authors.lastname: Popowska
authors.forename: Wiesława
authors.initials: W
authors.lastname: Grajkowska
authors.forename: Bozenna
authors.initials: B
authors.lastname: Dembowska-Bagińska
authors.forename: Ewa
authors.initials: E
authors.lastname: Kowalewska
authors.forename: Aneta
authors.initials: A
authors.lastname: Czajńska
authors.forename: Marta
authors.initials: M
authors.lastname: Perek-Polnik
authors.forename: Marcin
authors.initials: M
authors.lastname: Roszkowski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Syczewska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Danuta
authors.initials: D
authors.lastname: Perek
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
mesh_terms: D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010372:Pediatrics
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins