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The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma

Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key pr...

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Autores principales: Jovanović, Nikola, Mitrović, Tatjana, Cvetković, Vladimir J., Tošić, Svetlana, Vitorović, Jelena, Stamenković, Slaviša, Nikolov, Vesna, Kostić, Aleksandar, Vidović, Nataša, Krstić, Miljan, Jevtović-Stoimenov, Tatjana, Pavlović, Dušica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409652/
https://www.ncbi.nlm.nih.gov/pubmed/30717206
http://dx.doi.org/10.3390/medicina55020034
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author Jovanović, Nikola
Mitrović, Tatjana
Cvetković, Vladimir J.
Tošić, Svetlana
Vitorović, Jelena
Stamenković, Slaviša
Nikolov, Vesna
Kostić, Aleksandar
Vidović, Nataša
Krstić, Miljan
Jevtović-Stoimenov, Tatjana
Pavlović, Dušica
author_facet Jovanović, Nikola
Mitrović, Tatjana
Cvetković, Vladimir J.
Tošić, Svetlana
Vitorović, Jelena
Stamenković, Slaviša
Nikolov, Vesna
Kostić, Aleksandar
Vidović, Nataša
Krstić, Miljan
Jevtović-Stoimenov, Tatjana
Pavlović, Dušica
author_sort Jovanović, Nikola
collection PubMed
description Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients’ gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma.
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spelling pubmed-64096522019-03-25 The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma Jovanović, Nikola Mitrović, Tatjana Cvetković, Vladimir J. Tošić, Svetlana Vitorović, Jelena Stamenković, Slaviša Nikolov, Vesna Kostić, Aleksandar Vidović, Nataša Krstić, Miljan Jevtović-Stoimenov, Tatjana Pavlović, Dušica Medicina (Kaunas) Article Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients’ gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma. MDPI 2019-02-01 /pmc/articles/PMC6409652/ /pubmed/30717206 http://dx.doi.org/10.3390/medicina55020034 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jovanović, Nikola
Mitrović, Tatjana
Cvetković, Vladimir J.
Tošić, Svetlana
Vitorović, Jelena
Stamenković, Slaviša
Nikolov, Vesna
Kostić, Aleksandar
Vidović, Nataša
Krstić, Miljan
Jevtović-Stoimenov, Tatjana
Pavlović, Dušica
The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title_full The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title_fullStr The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title_full_unstemmed The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title_short The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
title_sort impact of mgmt promoter methylation and temozolomide treatment in serbian patients with primary glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409652/
https://www.ncbi.nlm.nih.gov/pubmed/30717206
http://dx.doi.org/10.3390/medicina55020034
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