Analiza odabranih markera glioblastroma
Committee membersJevtović-Stoimenov, Tatjana
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Glioblastomas (GBM) represent one of the most aggressive types of diffuse glioma. Although they usually arise as primary brain tumors, in 10% of GBM cases, they develop from low-grade astrocytomas (secondary GBM). They express striking morphological heterogeneity, which is often encountered during a histopathological examination. Due to advances in molecular diagnostics, significant progress was made in understanding the pathogenesis of tumor growth and the development of personalized therapeutic protocols. The aim of this study was to evaluate the diagnostic, prognostic, and predictive properties of the selected markers -IDH1/2 (isocitrate-dehydrogenase 1 and 2) mutation and MGMT (O6-methylguanine-DNA methyltransferase) and CHI3L1 (Chitinase-3-like protein 1) methylation status of the promoter regions in a Serbian population of GBM patients. Patients operated on the Neurosurgery Clinic (The University Clinical Centre of Niš, Serbia) between 2013 and 2019 were included in this study. S...anger direct sequencing was used to detect the presence of IDH1/2 mutations in samples and conventional and Real-Time methylation-specific polymerase chain reaction methods for methylation status evaluation. Age, the extent of tumor resection, and type of adjuvant chemotherapy were recognized as independent prognostic factors in GBM patients. Furthermore, results suggested the superiority of adjuvant Temozolomide over adjuvant chemotherapy with a nitrosourea-based protocol (PCV and BCNU). IDH1 mutation was detected in 6.67% (3/45) of patients and was associated with more prolonged overall survival, younger age, and hypermethylation of the MGMT and CHI3L1 promoter. Semi-quantitative MSP approaches resulted in improved detection sensitivity of MGMT methylation status compared to the qualitative MSP method. Among IDH-wt homogenous cohort of GBM patients older than 50 years with complete/partial resection of the tumor, overall survival of patients harboring highly methylated MGMT was significantly longer in comparison with the unmethylated group. Complementary evaluation of CHI3L1 promoter methylation status potentially increases the prognostic value of the MGMT methylation status, which should be further investigated in more comprehensive research.