MOLECULAR MARKERS IN PREDICTING THE OUTCOME OF DIFFUSE GLIOMA GRADE 4 TREATMENT

Abstract

Aim: To assess the expression of MGMT (O6-methylguanine-DNA methyltransferase) gene by MGMT RNA abundance and the presence of IDH1/2 (isocitrate dehydrogenase) variants in glioblastoma (GBM) samples for predicting the efficacy of temozolomide (TMZ) treatment, recurrence risk, and patients' survival.

Materials and methods: The expression of the MGMT gene and the presence of IDH1/2 variants were assessed by RT-PCR in tumor samples from 39 patients with histologically verified GBM or diffuse astrocytoma, grade 4. The number of MGMT RNA copies was determined by the calibration curves based on the pMA-RQ plasmid with the inserted MGMT gene.

Results: The number of MGMT RNA copies in GMB samples varied broadly from 1.7 to 88,270.2 copies per 1000 cells. The patients with a low level of MGMT expression (<1000 copies) in tumors had a more favorable prognosis for the TMZ treatment compared to the patients with a high level of MGMT RNA abundance (>10,000 copies). Among the patients included in the study, a wild type of IDH1/2 was detected in 36 cases, while 3 cases were IDH1 heterozygous.

Conclusion: The level of MGMT expression is considered a significant factor for prognosing GMB patients' survival. Patients with a low level of MGMT expression are considered candidates for efficient therapy with alkylating agents.