title: IDH1/2 Mutation and MGMT Promoter Methylation - the Relevant Survival Predictors in Czech Patients with Brain Gliomas.
abstract: Gliomas are a heterogeneous group of tumours varying in prognosis, treatment approach, and overall survival. Recently, novel markers have been identified which are linked to patient prognosis and therapeutic response. Especially the mutation of the enzyme isocitrate dehydrogenase 1 or 2 (IDH1/2) gene and the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status seem to be the most important predictors of survival. From 2012 to 2015, 94 Czech patients with primary brain tumours were enrolled into the study. The IDH1/2 mutation was detected by denaturing capillary electrophores.The methylation status of the MGMT gene and other 46 genes was revealed by MS-MLPA. In all 94 patients, the clinical data were correlated with molecular markers by Kaplan-Meier analyses and Cox regression model. The MGMT promoter methylation status was established and compared to clinical data. In our study eight different probes were used to elucidate the MGMT methylation status; hypermethylation was proclaimed if four and more probes were positive. This 3 : 5 ratio was tested and confirmed by Kaplan-Meier and Cox analyses. The study confirmed the importance of the IDH1/2 mutation and hypermethylation of the MGMT gene promoter being present in tumour tissue. Both markers are independent positive survival predictors; in the Cox model the IDH hazard ratio was 0.10 and in the case of MGMT methylation it reached 0.32. The methylation analysis of the panel of additional 46 genes did not reveal any other significant epigenetic markers; none of the candidate genes have been confirmed in the Cox regression analyses as an independent prognostic factor.
authors.affiliation: Department of Neurosurgery and Neurooncology, First Faculty of Medicine, Charles University and Military University Hospital Prague, Czech Republic.
authors.forename: F
authors.initials: F
authors.lastname: Kramář
authors.affiliation: Center for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Ltd, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Minárik
authors.affiliation: Center for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Ltd, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Benešová
authors.affiliation: Center for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Ltd, Prague, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Halková
authors.affiliation: Department of Neurosurgery and Neurooncology, First Faculty of Medicine, Charles University and Military University Hospital Prague, Czech Republic.
authors.forename: D
authors.initials: D
authors.lastname: Netuka
authors.affiliation: Department of Neurosurgery and Neurooncology, First Faculty of Medicine, Charles University and Military University Hospital Prague, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Bradáč
authors.affiliation: Department of Neurosurgery and Neurooncology, First Faculty of Medicine, Charles University and Military University Hospital Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Beneš
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D018153:Czech Republic; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D005910:Glioma / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes