Prognostic significance of MGMT promoter methylation in diffuse glioma patients
Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and...
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| Veröffentlicht in: | Biotechnology, biotechnological equipment biotechnological equipment, 2019-01, Vol.33 (1), p.639-644 |
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| creator | Jovanović, Nikola Mitrović, Tatjana Cvetković, Vladimir J. Tošić, Svetlana Vitorović, Jelena Stamenković, Slaviša Nikolov, Vesna Kostić, Aleksandar Vidović, Nataša Jevtović-Stoimenov, Tatjana Pavlović, Dušica |
| description | Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O
6
-methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidine-phosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers. |
| doi_str_mv | 10.1080/13102818.2019.1604158 |
| format | Article |
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6
-methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidine-phosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers.</description><identifier>ISSN: 1310-2818</identifier><identifier>EISSN: 1314-3530</identifier><identifier>DOI: 10.1080/13102818.2019.1604158</identifier><language>eng</language><publisher>Sofia: Taylor & Francis</publisher><subject>Alkylating agents ; Alkylation ; Chemoresistance ; Chemotherapy ; CpG ; CpG islands ; Cytotoxicity ; Deoxyribonucleic acid ; Diffuse glioma ; DNA ; DNA methylation ; DNA methyltransferase ; DNA repair ; Glioma cells ; Guanosine ; Methylguanine ; MGMT ; MSP ; O6-methylguanine-DNA methyltransferase ; overall survival ; Polymerase chain reaction ; prognosis ; Radiation ; Radiation therapy ; Spiders ; Survival ; Tumors</subject><ispartof>Biotechnology, biotechnological equipment, 2019-01, Vol.33 (1), p.639-644</ispartof><rights>2019 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science. 2019</rights><rights>2019 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-469e9d3d75a5fc9185b2da55e111d4c92734b869d36d2610b8cac876073a14473</citedby><cites>FETCH-LOGICAL-c451t-469e9d3d75a5fc9185b2da55e111d4c92734b869d36d2610b8cac876073a14473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/13102818.2019.1604158$$EPDF$$P50$$Ginformaworld$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/13102818.2019.1604158$$EHTML$$P50$$Ginformaworld$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,860,2096,27479,27901,27902,59116,59117</link.rule.ids></links><search><creatorcontrib>Jovanović, Nikola</creatorcontrib><creatorcontrib>Mitrović, Tatjana</creatorcontrib><creatorcontrib>Cvetković, Vladimir J.</creatorcontrib><creatorcontrib>Tošić, Svetlana</creatorcontrib><creatorcontrib>Vitorović, Jelena</creatorcontrib><creatorcontrib>Stamenković, Slaviša</creatorcontrib><creatorcontrib>Nikolov, Vesna</creatorcontrib><creatorcontrib>Kostić, Aleksandar</creatorcontrib><creatorcontrib>Vidović, Nataša</creatorcontrib><creatorcontrib>Jevtović-Stoimenov, Tatjana</creatorcontrib><creatorcontrib>Pavlović, Dušica</creatorcontrib><title>Prognostic significance of MGMT promoter methylation in diffuse glioma patients</title><title>Biotechnology, biotechnological equipment</title><description>Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O
6
-methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidine-phosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers.</description><subject>Alkylating agents</subject><subject>Alkylation</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>CpG</subject><subject>CpG islands</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Diffuse glioma</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA methyltransferase</subject><subject>DNA repair</subject><subject>Glioma cells</subject><subject>Guanosine</subject><subject>Methylguanine</subject><subject>MGMT</subject><subject>MSP</subject><subject>O6-methylguanine-DNA methyltransferase</subject><subject>overall survival</subject><subject>Polymerase chain reaction</subject><subject>prognosis</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Spiders</subject><subject>Survival</subject><subject>Tumors</subject><issn>1310-2818</issn><issn>1314-3530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNp9UU1PHDEMHVUgla-fgBSJ82ztfE3mVoSAIoHgAOcom49tVjOTJZkV2n_fLEt77MmW_fzs59c0lwgLBAU_kCFQhWpBAfsFSuAo1LfmpNZ5ywSDo88c2j3oe3NayhqgA8DupHl-yWk1pTJHS0pcTTFEaybrSQrk6f7plWxyGtPsMxn9_Hs3mDmmicSJuBjCtniyGmIaDdnUhp_mct4cBzMUf_EVz5q3u9vXm1_t4_P9w831Y2u5wLnlsve9Y64TRgTboxJL6owQHhEdtz3tGF8qWSHSUYmwVNZY1UnomEHOO3bWPBx4XTJrvclxNHmnk4n6s5DySptcRQ1eg6RS9R1yxQSnVBoFwsklD8ZS1aOpXFcHrqr1fevLrNdpm6d6vqZMIAhKFasocUDZnErJPvzbiqD3Pui_Pui9D_rLhzr38zAXp5DyaD5SHpyezW5IOeT661g0-z_FH3_pjKU</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Jovanović, Nikola</creator><creator>Mitrović, Tatjana</creator><creator>Cvetković, Vladimir J.</creator><creator>Tošić, Svetlana</creator><creator>Vitorović, Jelena</creator><creator>Stamenković, Slaviša</creator><creator>Nikolov, Vesna</creator><creator>Kostić, Aleksandar</creator><creator>Vidović, Nataša</creator><creator>Jevtović-Stoimenov, Tatjana</creator><creator>Pavlović, Dušica</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7ST</scope><scope>7XB</scope><scope>8FD</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>SOI</scope><scope>DOA</scope></search><sort><creationdate>20190101</creationdate><title>Prognostic significance of MGMT promoter methylation in diffuse glioma patients</title><author>Jovanović, Nikola ; Mitrović, Tatjana ; Cvetković, Vladimir J. ; Tošić, Svetlana ; Vitorović, Jelena ; Stamenković, Slaviša ; Nikolov, Vesna ; Kostić, Aleksandar ; Vidović, Nataša ; Jevtović-Stoimenov, Tatjana ; Pavlović, Dušica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-469e9d3d75a5fc9185b2da55e111d4c92734b869d36d2610b8cac876073a14473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alkylating agents</topic><topic>Alkylation</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>CpG</topic><topic>CpG islands</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>Diffuse glioma</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA methyltransferase</topic><topic>DNA repair</topic><topic>Glioma cells</topic><topic>Guanosine</topic><topic>Methylguanine</topic><topic>MGMT</topic><topic>MSP</topic><topic>O6-methylguanine-DNA methyltransferase</topic><topic>overall survival</topic><topic>Polymerase chain reaction</topic><topic>prognosis</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>Spiders</topic><topic>Survival</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jovanović, Nikola</creatorcontrib><creatorcontrib>Mitrović, Tatjana</creatorcontrib><creatorcontrib>Cvetković, Vladimir J.</creatorcontrib><creatorcontrib>Tošić, Svetlana</creatorcontrib><creatorcontrib>Vitorović, Jelena</creatorcontrib><creatorcontrib>Stamenković, Slaviša</creatorcontrib><creatorcontrib>Nikolov, Vesna</creatorcontrib><creatorcontrib>Kostić, Aleksandar</creatorcontrib><creatorcontrib>Vidović, Nataša</creatorcontrib><creatorcontrib>Jevtović-Stoimenov, Tatjana</creatorcontrib><creatorcontrib>Pavlović, Dušica</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Environment Abstracts</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Biotechnology, biotechnological equipment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jovanović, Nikola</au><au>Mitrović, Tatjana</au><au>Cvetković, Vladimir J.</au><au>Tošić, Svetlana</au><au>Vitorović, Jelena</au><au>Stamenković, Slaviša</au><au>Nikolov, Vesna</au><au>Kostić, Aleksandar</au><au>Vidović, Nataša</au><au>Jevtović-Stoimenov, Tatjana</au><au>Pavlović, Dušica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic significance of MGMT promoter methylation in diffuse glioma patients</atitle><jtitle>Biotechnology, biotechnological equipment</jtitle><date>2019-01-01</date><risdate>2019</risdate><volume>33</volume><issue>1</issue><spage>639</spage><epage>644</epage><pages>639-644</pages><issn>1310-2818</issn><eissn>1314-3530</eissn><abstract>Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O
6
-methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidine-phosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers.</abstract><cop>Sofia</cop><pub>Taylor & Francis</pub><doi>10.1080/13102818.2019.1604158</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alkylating agents Alkylation Chemoresistance Chemotherapy CpG CpG islands Cytotoxicity Deoxyribonucleic acid Diffuse glioma DNA DNA methylation DNA methyltransferase DNA repair Glioma cells Guanosine Methylguanine MGMT MSP O6-methylguanine-DNA methyltransferase overall survival Polymerase chain reaction prognosis Radiation Radiation therapy Spiders Survival Tumors |
| title | Prognostic significance of MGMT promoter methylation in diffuse glioma patients |
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