gms | German Medical Science

Objective: Approximately 80% of primary glioblastomas (pGBM) harbor activating TERT promoter mutations. TERT activity is also influenced by a common functional polymorphism of the gene (rs2853669). MGMT promoter hypermethylation is found in >40% of cases. Treatment decisions are increasingly based on MGMT methylation analysis results. For the present paper, we have explored possible correlations between MR imaging characteristics, TERT mutations, MGMT promoter methylation status, and rs2853669 genotypes.

Method: The pre-operative MR images of 64 primary GBM patients were retrospectively analyzed. We divided the human brain into 26 regions per hemisphere in order to assess tumor location and extension. A region was considered to be involved if at least 1/3 of it was tumor infiltrated or comprised 1/3 of the total tumor volume based on T1w contrast-enhanced images. The following additional characteristics were recorded: involved hemisphere; midline shift < 1cm; subependymal spread; monofocal vs. multifocal growth; presence of tumor satellites. We also measured vital tumor (defined by T1w contrast-enhanced 3D sequences) and necrosis volume (based on T2w images) using Intellispace Software (Philips Healthcare). TERT mutation status/rs2853669 polymorphism genotypes and MGMT promoter methylation status were assessed using direct sequencing and pyrosequencing, respectively. Presumed correlations between molecular genetic findings and imaging data were tested for statistical significance using standard methods as indicated (IBM SPSS 22.0).

Results: TERT mutations were identified in 50/64 cases (78.1%). MGMT promoter hypermethylation was found in 25/52 tumors (48.1%). Neither TERT mutations, nor MGMT promoter methylation status or rs2853669 genotypes were found to correlate significantly with any of the investigated MRI characteristics including tumor location, vital tumor volume and tumor/necrosis ratio. Specifically, there was no association between the molecular genetic findings and tumor growth in the periventricular zone.

Conclusions: The role of molecular genetic markers in the clinical management of gliomas is increasing. Hence, their non-invasive (i.e. neuroradiological) assessment is a very promising field for research. Unfortunately, the present study fails to identify specific neuroimaging findings on standard MRIs associated with two important molecular genetic alterations, i.e. TERT mutations and MGMT promoter methylation.