Progrese glial tümörlerde mgmt (metil guanin-dna metil transferaz) metilasyonu ve ıdh (izositrat dehidrojenaz) mutasyonunda değişimin incelenmesi ve prognoza etkisinin araştırılması

INTRODUCTION and PURPOSE: 06- methylguanine DNA methyltransferase (MGMT) enzyme which is synthesized in glial tumors, repairs DNA damage that is generated by nitrosourea compounds. Isocitrate dehydrogenase (IDH) is an enzyme of Krebs cycle in the cell. Both MGMT methylation status and IDH gene mutation is known to affect the prognosis in gliomas. The aims of this thesis are to determine whether MGMT methylation status and IDH mutation status changes during progression and to demonstrate any possible effect of this change on survival in progressed glial tumors. MATERIALS and METHODS: 52 patients with relapsed/progressed glial tumors who admitted to Yeditepe University Hospital between January 2007 and June 2014 were screened in this retrospective cross-sectional study and 44 of them were included as they had pathology slides appropriate for pathological evaluation. MGMT methylation status and IDH mutation status was evaluated by an expert pathologist with immunohistochemical methods. RESULTS: MGMT were found to be methylated in 14 of 44 patients (31.8%) at first diagnosis. In 6 of 14 (42,9%) patients with methylated MGMT at first diagnosis, conversion to unmethylated status was observed and in 6 of 30 (20%) patients with unmethylated MGMT, conversion to methylated status was observed at relapse/progression. Median overall survival times were 23 vs. 45 months in patients with MGMT methylated and unmethylated at diagnosis, respectively. IDH1 was found to be mutated in 12 of 44 patients (27.3%) at first diagnosis. One of these patients (8.3%) converted to IDH1-unmutated state, while 5 of 32 (15.6%) IDH non-mutant patients were found to be IDH mutant at relapse/progression. Median overall survival were 52 vs. 31 months in patients with IDH1 mutated and non-mutated at diagnosis, respectively. CONCLUSIONS: MGMT methylation and IDH1 mutation status did not appear to change significantly at progression in glial tumors. There was no statistically significant difference in median overall survival between MGMT methylated and unmethylated patients at the diagnosis, while IDH mutated patients at diagnosis had longer survival than non-mutated patients.