title: Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma.
abstract: We investigated the role of somatic mutations and a common single nucleotide polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT expression was analyzed by quantitative real time-PCR. The association between hTERT promoter genetic changes and other genomic events and clinical variables common in gliomas were examined. C228T and C250T somatic mutations were found in 60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic mutations and the SNP likely have opposing effects on hTERT expression. hTERT expression was significantly higher in the C228T or C250T mutated tumors. Tumors with the T349C genotype showed lower hTERT expression when C228T or C250T mutations were present. However, no significant survival differences were observed among the groups with or without hTERT promoter mutations and SNP. There was a significant association between genetic changes in the hTERT promoter and patient age as well as MGMT promoter methylation and EGFR amplification. hTERT expression is modulated by somatic mutations in the hTERT promoter as well as a common polymorphism. However, hTERT related genomic changes have limited value as an independent prognostic factor for clinical outcomes in glioblastomas.
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;Department of Biomedical Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Ja Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D019098:Telomerase