title: IDH1/IDH2 but not TP53 mutations predict prognosis in Bulgarian glioblastoma patients.
abstract: Mutations in genes encoding isocitrate dehydrogenase isoforms 1 (IDH1) and 2 (IDH2) have been associated with good prognosis for patients with brain neoplasias and have been commonly found together with mutated TP53 gene. To determine the prevalence of IDH1, IDH2, and TP53 mutations and their impact on overall survival 106 glioblastoma patients were analysed. IDH1 mutations were detected in 13 and IDH2 mutation in one patient. Two homozygous samples with R132H mutation in IDH1 gene and a novel aberration K129R in IDH2 gene were found. Sixty-four percent of IDH1/IDH2 mutated tumours harboured also a mutation in TP53 gene. Genetic aberrations in TP53 were present in 37 patients. Statistical analysis of the impact of the studied factors on the overall survival showed that the mutations in IDH1/IDH2, but not the ones in TP53, were associated with longer survival. Also, the impact of age on prognosis was confirmed. This is the first comprehensive study on glioblastomas in Bulgaria. Our results suggest that IDH1/IDH2 but not TP53 mutations together with other prognostic factors such as age might be applied in clinical practice for prediction of outcome in patients with glioblastomas.
authors.affiliation: Molecular Medicine Center, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria ; Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
authors.forename: Gergana
authors.initials: G
authors.lastname: Stancheva
authors.affiliation: Molecular Medicine Center, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
authors.forename: Teodora
authors.initials: T
authors.lastname: Goranova
authors.affiliation: Department of Neurosurgery, University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov", 21 Totleben Boulevard, 1606 Sofia, Bulgaria.
authors.forename: Maria
authors.initials: M
authors.lastname: Laleva
authors.affiliation: Department of Pathology, University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov", 21 Totleben Boulevard, 1606 Sofia, Bulgaria.
authors.forename: Margarita
authors.initials: M
authors.lastname: Kamenova
authors.affiliation: Molecular Medicine Center, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria ; Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
authors.forename: Atanaska
authors.initials: A
authors.lastname: Mitkova
authors.affiliation: Department of Neurosurgery, University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov", 21 Totleben Boulevard, 1606 Sofia, Bulgaria.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Velinov
authors.affiliation: Department of Neurosurgery, University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov", 21 Totleben Boulevard, 1606 Sofia, Bulgaria.
authors.forename: George
authors.initials: G
authors.lastname: Poptodorov
authors.affiliation: Molecular Medicine Center, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria ; Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
authors.affiliation: Molecular Medicine Center, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria ; Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.affiliation: Department of Neurosurgery, University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov", 21 Totleben Boulevard, 1606 Sofia, Bulgaria.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Gabrovsky
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002031:Bulgaria; D002869:Chromosome Aberrations; D005260:Female; D016158:Genes, p53; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human