Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , |
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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oai:revistas.usp.br:article/19488 |
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USP-19 |
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Clinics |
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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 |
_version_ |
1800222757345034240 |