DETERMINATION OF MOLECULAR GENETIC MARKERS IN PROGNOSIS OF THE EFFECTIVENESS OF TREATMENT OF MALIGNANT INTRACEREBRAL BRAIN TUMORS

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

Abstract


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.

Keywords


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

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DOI: http://dx.doi.org/10.21303/2504-5679.2019.00949

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