Oleksandr Glavatskyi, Irina Vasileva, Olena Galanta, Hennadii Khmelnytskyi, Irina Shuba, Konstantin Kardash, Oksana Zemskova


Intracerebral malignant brain tumors remain one of the most complex problems of neuro-oncology. Today, promising results of the use of targeted drugs have been received, which determine the important diagnostic and predictive value of molecular genetic markers of glial and metastatic brain tumors.

Aim: The study of the prevalence of MGMT (O6-methylguanine-DNA methyltransferase) and PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene expression by real time polymerase chain reaction in tumor tissue of gliomas and brain metastases.

Materials and methods: From thirty patients were received tumor material (29 cases of glioma III-IV degree of anaplasia and one case of metastatic brain lesion of adenocarcinoma). The normalized expression of MGMT and PTEN genes was determined by real-time polymerase chain reaction.

Results: In all 30 (100 %) patients with tumor fragments, we determined normalized expression of MGMT and PTEN genes. In most cases, 53 % of the observations (16 out of 30 patients) showed a low normalized expression of MGMT gene (<40 c. u.) and a low normalized PTEN expression rate of 73 % (22 out of 30 patients) (<40 c. u.). The average expression level of the MGMT gene in the range from 40 to 100 c. u. (6/20 % of patients) was considered prognostic favourable for the response to temozolomide chemotherapy.

Conclusions: The study of MGMT gene expression, a chemotherapy marker for temozolomide, indicates a trend toward correlation between expression levels and therapeutic efficacy. The study of the expression of the PTEN gene, the blocker of the PI3K / AKT signal pathway, indicates a different degree of expression of this enzyme in the tumour samples studied. The predictive value of the indicator for target therapy is appropriate in comparison with the EGFR mutation. Further profound analysis of the results is required with increasing number of sampling and observation period.


malignant brain tumors; glioblastoma; MGMT gene; PTEN gene; EGFR; personalized medicine

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Nørøxe, D. S., Poulsen, H. S., Lassen, U. (2016). Hallmarks of glioblastoma: a systematic review. ESMO Open, 1 (6), e000144. doi:

Wick, W., Osswald, M., Wick, A., Winkler, F. (2018). Treatment of glioblastoma in adults. Therapeutic Advances in Neurological Disorders, 11. doi:

Walker, M. D., Alexander, E., Hunt, W. E., MacCarty, C. S., Mahaley, M. S., Mealey, J. et. al. (1978). Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. Journal of Neurosurgery, 49 (3), 333–343. doi:

Walker, M. D., Green, S. B., Byar, D. P., Alexander, E., Batzdorf, U., Brooks, W. H. et. al. (1980). Randomized Comparisons of Radiotherapy and Nitrosoureas for the Treatment of Malignant Glioma after Surgery. New England Journal of Medicine, 303 (23), 1323–1329. doi:

Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B. et. al. (2005). Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352 (10), 987–996. doi:

Holland, E., Ene, C. (2015). Personalized Medicine for Gliomas. Surgical Neurology International, 6 (2), 89–95. doi:

Jiapaer, S., Furuta, T., Tanaka, S., Kitabayashi, T., Nakada, M. (2018). Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma. Neurologia Medico-Chirurgica, 58 (10), 405–421. doi:

Lee, S. Y. (2016). Temozolomide resistance in glioblastoma multiforme. Genes & Diseases, 3 (3), 198–210. doi:

Wang, J., Hu, G., Quan, X. (2019). Analysis of the factors affecting the prognosis of glioma patients. Open Medicine, 14 (1), 331–335. doi:

Hartmann, C., Hentschel, B., Simon, M., Westphal, M., Schackert, G. et. al. (2013). Long-Term Survival in Primary Glioblastoma With Versus Without Isocitrate Dehydrogenase Mutations. Clinical Cancer Research, 19 (18), 5146–5157. doi:

Reifenberger, G., Weber, R. G., Riehmer, V., Kaulich, K., Willscher, E. et. al. (2014). Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling. International Journal of Cancer, 135 (8), 1822–1831. doi:

Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K. et. al. (2016). The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica, 131 (6), 803–820. doi:

Medina, T. M., Lewis, K. D. (2016). The evolution of combined molecular targeted therapies to advance the therapeutic efficacy in melanoma: a highlight of vemurafenib and cobimetinib. OncoTargets and Therapy, 9, 3739–3752. doi:

Xiao, W.-Z., Han, D.-H., Wang, F., Wang, Y.-Q., Zhu, Y.-H., Wu, Y.-F. et. al. (2014). Relationships between PTEN gene mutations and prognosis in glioma: a meta-analysis. Tumor Biology, 35 (7), 6687–6693. doi:

Brandes, A. A., Franceschi, E., Paccapelo, A., Tallini, G., De Biase, D., Ghimenton, C. et. al. (2017). Role of MGMT Methylation Status at Time of Diagnosis and Recurrence for Patients with Glioblastoma: Clinical Implications. The Oncologist, 22 (4), 432–437. doi:

Nguyen, H., Shabani, S., Awad, A., Kaushal, M., Doan, N. (2018). Molecular Markers of Therapy-Resistant Glioblastoma and Potential Strategy to Combat Resistance. International Journal of Molecular Sciences, 19 (6), 1765. doi:

Kwatra, M. (2017). A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma. Current Cancer Drug Targets, 17 (3), 290–296. doi:

Liu, F., Mischel, P. S. (2017). Targeting epidermal growth factor receptor co-dependent signaling pathways in glioblastoma. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 10 (1), e1398. doi:

Eskilsson, E., Røsland, G. V., Solecki, G., Wang, Q., Harter, P. N., Graziani, G. et. al. (2017). EGFR heterogeneity and implications for therapeutic intervention in glioblastoma. Neuro-Oncology, 20 (6), 743–752. doi:

Elsamadicy, A. A., Chongsathidkiet, P., Desai, R., Woroniecka, K., Farber, S. H., Fecci, P. E., Sampson, J. H. (2017). Prospect of rindopepimut in the treatment of glioblastoma. Expert Opinion on Biological Therapy, 17 (4), 507–513. doi:

Benitez, J. A., Ma, J., D’Antonio, M., Boyer, A., Camargo, M. F., Zanca, C. et. al. (2017). PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3. Nature Communications, 8 (1). doi:

Kang, Y.-J., Balter, B., Csizmadia, E., Haas, B., Sharma, H., Bronson, R., Yan, C. T. (2017). Erratum: Corrigendum: Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival. Nature Communications, 8 (1). doi:



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