title: The correlation between promoter methylation status and the expression level of O6-methylguanine-DNA methyltransferase in recurrent glioma.
abstract: BACKGROUND
  The DNA repair protein O(6)-methylguanine-DNA methyltransferase is a drug-resistant protein, which protects the tumors from chemotherapeutic alkylating agents, such as temozolomide. The methylation status of O(6)-methylguanine-DNA methyltransferase promoter has been shown to be a major predictive factor for clinical outcome in glioma patients when treated by alkylating agents. Thereby, there were many reports on O(6)-methylguanine-DNA methyltransferase promoter methylation and mRNA expression in primary glioma, in contrast, there were only a few studies in recurrent glioma.
  
  
  METHODS
  We evaluated the O(6)-methylguanine-DNA methyltransferase mRNA expression and promoter methylation status in glioma patients before and after recurrence by quantitative real-time PCR and methylation-specific PCR assay. Thirteen paired primary and recurrent glioma patients were analyzed, including four patients in whom malignant transformation occurred from Grade II to Grade III.
  
  
  RESULTS
  Methylation-specific PCR assay demonstrated that the status of O(6)-methylguanine-DNA methyltransferase promoter changed from methylated to unmethylated in 10 of 13 samples when the tumor relapsed. Moreover, intra-individual O(6)-methylguanine-DNA methyltransferase mRNA level increased in recurrent gliomas than in primary ones (P = 0.016). O(6)-methylguanine-DNA methyltransferase mRNA level was correlated with the methylation status (P = 0.012).
  
  
  CONCLUSIONS
  Our results give the evidence that the increase of O(6)-methylguanine-DNA methyltransferase mRNA expression caused by methylation changes in recurrence may be associated with chemoresistance in the recurrent glioma.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641 Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakada
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Emi
authors.initials: E
authors.lastname: Nambu
authors.forename: Natsuki
authors.initials: N
authors.lastname: Furuyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Hamada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D019175:DNA Methylation; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012333:RNA, Messenger; D019853:O(6)-Methylguanine-DNA Methyltransferase