Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
Ραζή Ευαγγελία, Διευθύντρια Γ’ Ογκολογικής Κλινικής, Νοσοκομείο «ΥΓΕΙΑ»
Βαϊόπουλος Γεώργιος, Καθηγητής, Ιατρική, ΕΚΠΑ
BACKGROUND: Gliomas are the most common malignant brain tumors in adults. The use of molecular markers to further characterize gliomas is included in their classification, but is also useful in the choice of a therapeutic approach. In addition to widely used markers, such as IDH, MGMT and 1p19q, the role of mutations in TERT (Telomerase Reverse Transcriptase) gene is currently being studied. With a higher prevalence in glioblastoma, TERT mutations play a different prognostic role in higher and lower malignant gliomas. Trying to further determine its role, attempts have been made to correlate TERT with other molecular markers. This study was designed to investigate the role of TERT mutations in glioma patients.
MATERIALS AND METHODS: In the present study 115 patients at a median age of 46 years diagnosed with malignant glioma were studied from 2004 to 2017. For those patients, we had information on their clinical and pathological characteristics, on their therapy and on the following molecular markers: IDH1 expression (IHC or PCR), MGMT methylation (PCR), BRAF status (IHC or PCR), expression of EGFRvIII (IHC or real time PCR), expression of ATRX (IHC), co-deletion of 1p/19q (MLPA), p53 expression (IHC). After collecting formalin-fixed paraffin-embedded (FFPE) tumor samples, laboratory and clinical data were recorded. After isolation of DNA from the biopsy, TERT mutation analysis was performed using the Nested PCR technique. Finally, sequence analysis was performed by Sanger sequencing.
RESULTS: Median overall survival was 33,5 months for all patients, while glioblastoma patients had the worst survival (20,9 months). The prognostic role of the mutation of IDH and the methylation of MGMT was confirmed. The most common TERT mutation was C228T, followed by C250T. Patients with a TERT mutation in this study usually were older, they were diagnosed with glioblastoma or oligodendroglioma rather than astrocytoma and they were usually found to be IDH wild-type which seems to play the most crucial role concerning their survival. TERT promoter mutation was a negative prognostic factor for all patients in this study, which was also the case for high grade gliomas while we were not able to take any safe conclusion regarding low grade gliomas.
CONCLUSION: The prognostic role of TERT concerning both the histological subtype of glioma and the other molecular markers has been demonstrated in this rather representative study. The potential therapeutic targeting of TERT and the study of its predictive role in both chemotherapy and radiotherapy will be the main pillars of further research.
Glioma, TERT, Mutation, Biomarkers, Oncology