title: Identification of MGMT promoter methylation sites correlating with gene expression and IDH1 mutation in gliomas.
abstract: O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation was reported to be an independent prognostic and predictive factor in glioma patients who received temozolomide treatment. However, the predictive value of MGMT methylation was recently questioned by several large clinical studies. The purpose of this study is to identify MGMT gene promoter CpG sites or region whose methylation were closely correlated with its gene expression to elucidate this contradictory clinical observations. The methylation status for all CpG dinucleotides in MGMT promoter and first exon region were determined in 42 Chinese glioma patients, which were then correlated with MGMT gene expression, IDH1 mutation, and tumor grade. In whole 87 CpG dinucleotides analyzed, three distinct CpG regions covering 28 CpG dinucleotides were significantly correlated with MGMT gene expression; 10 CpG dinucleotides were significantly correlated with glioma classification (p < 0.05). Isocitrate dehydrogenase 1 (IDH1) mutation and MGMT gene hypermethylation significantly co-existed, but not for MGMT gene expression. The validation cohort of gliomas treated with standard of care and comparison of the CpGs we identified with the current CpGs used in clinical setting will be very important for gliomas individual medicine in the future.
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Yang
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Quan
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Kang
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China. daipg@nuw.edu.cn.
authors.forename: Peng-Gao
authors.initials: PG
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Correlation analysis; Glioma; IDH1; MGMT; Methylation; Pyrosequencing