Abstract
Background
Telomerase Reverse Transcriptase (TERT) is increasingly important in the molecular characterization of malignant gliomas. Its role differs between low and high grade gliomas and its association with other biomarkers and treatment outcome is still under investigation.
Material and Methods
In the present study, 115 patients at a median age of 46 years diagnosed from 2004 to 2017 with malignant glioma were studied. For all patients, we had information on their clinical and pathological characteristics, on their therapy and on: IDH1 expression (IHC or PCR), MGMT methylation (PCR), BRAF expression (IHC or PCR), expression of EGFRvIII (IHC or real time PCR), expression of ATRX (IHC), co-deletion of 1p/19q (MLPA), p53 expression (IHC). For TERT, DNA was isolated from formalin fixed paraffin embedded tissue and mutation analysis was performed using Nested PCR. Finally, sequence analysis was performed by Sanger sequencing.
Results
Of the 115 patients 77 were diagnosed with GBM, 11 with an astrocytoma grade III and 9 with an astrocytoma grade II, while 9 had grade III oligodendroglioma and 3 grade II oligodendroglioma. Median overall survival was 33,5 months for all patients, while glioblastoma patients had the worst survival (20,9 months). Patients with a mutation in IDH1 had a median overall survival of 78,8 months, much longer than the 42 months of IDH wild-type patients. Glioma patients with an MGMT methylation had also a longer median overall survival (42,7 months) than those with unmethylated MGMT (20,3 months). TERT promoter mutations were observed in 75 out of 115 patients. Of these, C228T mutation was detected in 59 patients, C250T mutation in 15 and C127 mutation in only 1 patient. Patients with a TERT mutation were older, they were diagnosed with glioblastoma or oligodendroglioma rather than astrocytoma and they were usually found to be IDH wild-type, the latter being the parameter most significantly associated with survival. TERT promoter mutation was a negative prognostic factor for the entire population, as well as for the 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 axes of further research.