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Methylation of the O-6-methylguanine-DNA methyltransferase ( MGMT ) gene promoter is currently the most important prognostic biomarker in therapy of IDH-wild-type glioblastoma. One can obtain information about this methylation from total DNA methylation profile., Objective: To analyze the DNA methylation signal intensity in the MGMT gene in samples of malignant gliomas and identify the most significant genomic positions for calculating the MGMT gene promoter status for further improvement of diagnostics and prediction of therapeutic options in patients with malignant gliomas., Material and Methods: The study is based on 43 samples (frozen tissue or paraffin blocks) from patients with malignant gliomas. Tumor DNA samples were prepared using the Illumina Infinium MethylationEPIC BeadChip Kit and the Illumina Next-Seq 550 Sequencing System platform. DNA methylation profiles were analyzed using computational algorithms in the R language, specialized libraries minfi and mgmtstp27, as well as basic statistical functions in the Rstudio environment., Results: We established the MGMT gene promoter status in 43 samples of malignant gliomas considering total DNA methylation profile. In 24 samples (55%), the MGMT gene promoter was methylated. We compared methylation signal in certain CpG islands in groups with methylated and unmethylated MGMT gene promoters and identified the most significant positions for further improvement of data analysis algorithm., Conclusion: These data demonstrate the possibilities and prospects for further improvement of algorithm for analysis of the MGMT gene promoter status based on total DNA methylation profile in patients with malignant gliomas as an alternative to methyl-specific PCR. Our results are consistent with data of other neuro-oncology researchers. Indeed, computational methods like MGMT-STP27 are quite powerful and can be used in scientific and clinical practice to assess prognosis and make decisions about chemotherapy with alkylating agents.

Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.

Objective: To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH -negative diffuse astrocytomas grade III (anaplastic gliomas)., Material and Methods: The study included 45 patients aged 45.5 years. Forty-two patients underwent resection of tumor, other 3 ones - stereotactic biopsy. TERT mutation was identified in 21 patients. External beam radiation therapy was performed in 35 patients (60 Gy), chemotherapy - in 34 patients (mainly temozolomide). Follow-up data were available in 44 patients., Results: Median of overall survival in patients with TERT mutation was 15.3 months, in patients with TERT -negative tumors - 65.1 months. Median of relapse-free survival in patients with TERT-positive anaplastic astrocytoma (AA) was 13.3 months, in patients with TERT -negative glioma - 57.7 months. These differences were not significant. Relapse-free survival was higher in patients with AA and no TERT mutation at all intervals, but especially at early stages (12 and 24 months)., Conclusion: Inclusion of TERT mutation in mandatory examination panel for gliomas in general and, in particular, gliomas grade II/III without IDH mutation can lead to sub-classification of these tumors in the near future. Routine analysis of TERT mutation in these patients will be valuable for correct medical consultation regarding prognosis and adequate adjuvant treatment.

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

Diffuse midline gliomas are relatively rare in adults. Regardless of age, all diffuse midline gliomas are routinely examined in our Center for the presence of the H3F3A K27M gene mutation. However, we identified IDH -mutant brainstem glioma in a 42-year-old man for the first time.