Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

Detalhes bibliográficos
Autor(a) principal: Uno, Miyuki
Data de Publicação: 2011
Outros Autores: Oba-Shinjo, Sueli Mieko, Camargo, Anamaria Aranha, Moura, Ricardo Pereira, Aguiar, Paulo Henrique de, Cabrera, Hector Navarro, Begnami, Marcos, Rosemberg, Sérgio, Teixeira, Manoel Jacobsen, Marie, Suely Kazue Nagahashi
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Clinics
Texto Completo: https://www.revistas.usp.br/clinics/article/view/19488
Resumo: OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.
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spelling Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma GlioblastomaMGMT promoter methylationMGMT geneMGMT proteinPrognosis OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue. Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2011-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/1948810.1590/S1807-59322011001000013Clinics; Vol. 66 No. 10 (2011); 1747-1755 Clinics; v. 66 n. 10 (2011); 1747-1755 Clinics; Vol. 66 Núm. 10 (2011); 1747-1755 1980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/19488/21551Uno, MiyukiOba-Shinjo, Sueli MiekoCamargo, Anamaria AranhaMoura, Ricardo PereiraAguiar, Paulo Henrique deCabrera, Hector NavarroBegnami, MarcosRosemberg, SérgioTeixeira, Manoel JacobsenMarie, Suely Kazue Nagahashiinfo:eu-repo/semantics/openAccess2012-05-23T16:43:30Zoai:revistas.usp.br:article/19488Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2012-05-23T16:43:30Clinics - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
title Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
spellingShingle Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
Uno, Miyuki
Glioblastoma
MGMT promoter methylation
MGMT gene
MGMT protein
Prognosis
title_short Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
title_full Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
title_fullStr Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
title_full_unstemmed Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
title_sort Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
author Uno, Miyuki
author_facet Uno, Miyuki
Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
Aguiar, Paulo Henrique de
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
author_role author
author2 Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
Aguiar, Paulo Henrique de
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Uno, Miyuki
Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
Aguiar, Paulo Henrique de
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
dc.subject.por.fl_str_mv Glioblastoma
MGMT promoter methylation
MGMT gene
MGMT protein
Prognosis
topic Glioblastoma
MGMT promoter methylation
MGMT gene
MGMT protein
Prognosis
description OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.
publishDate 2011
dc.date.none.fl_str_mv 2011-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/clinics/article/view/19488
10.1590/S1807-59322011001000013
url https://www.revistas.usp.br/clinics/article/view/19488
identifier_str_mv 10.1590/S1807-59322011001000013
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/clinics/article/view/19488/21551
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
dc.source.none.fl_str_mv Clinics; Vol. 66 No. 10 (2011); 1747-1755
Clinics; v. 66 n. 10 (2011); 1747-1755
Clinics; Vol. 66 Núm. 10 (2011); 1747-1755
1980-5322
1807-5932
reponame:Clinics
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Clinics
collection Clinics
repository.name.fl_str_mv Clinics - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||clinics@hc.fm.usp.br
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