title: Mutation of the uracil DNA glycosylase gene detected in glioblastoma.
abstract: Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Y W
authors.initials: YW
authors.lastname: Moon
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: A O
authors.initials: AO
authors.lastname: Vortmeyer
authors.forename: R J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: T A
authors.initials: TA
authors.lastname: Winters
authors.forename: Z
authors.initials: Z
authors.lastname: Zhuang
authors.forename: B G
authors.initials: BG
authors.lastname: Fuller
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics*; D045647:DNA Glycosylases; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D009837:Oligodendroglioma / Q000201:enzymology / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured; D051981:Uracil-DNA Glycosidase
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase