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

OBJECTIVES: 1) To correlate the methylation status of the O(6)-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 gliobl...

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Autores principales: Uno, Miyuki, Oba-Shinjo, Sueli Mieko, Camargo, Anamaria Aranha, Moura, Ricardo Pereira, de Aguiar, Paulo Henrique, Cabrera, Hector Navarro, Begnami, Marcos, Rosemberg, Sérgio, Teixeira, Manoel Jacobsen, Marie, Suely Kazue Nagahashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180167/
https://www.ncbi.nlm.nih.gov/pubmed/22012047
http://dx.doi.org/10.1590/S1807-59322011001000013
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author Uno, Miyuki
Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
de Aguiar, Paulo Henrique
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
author_facet Uno, Miyuki
Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
de Aguiar, Paulo Henrique
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
author_sort Uno, Miyuki
collection PubMed
description OBJECTIVES: 1) To correlate the methylation status of the O(6)-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 pubmed-31801672011-10-01 Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma Uno, Miyuki Oba-Shinjo, Sueli Mieko Camargo, Anamaria Aranha Moura, Ricardo Pereira de Aguiar, Paulo Henrique Cabrera, Hector Navarro Begnami, Marcos Rosemberg, Sérgio Teixeira, Manoel Jacobsen Marie, Suely Kazue Nagahashi Clinics (Sao Paulo) Clinical Science OBJECTIVES: 1) To correlate the methylation status of the O(6)-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 da Faculdade de Medicina da Universidade de São Paulo 2011-10 /pmc/articles/PMC3180167/ /pubmed/22012047 http://dx.doi.org/10.1590/S1807-59322011001000013 Text en Copyright © 2011 Hospital das Clínicas da FMUSP http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Science
Uno, Miyuki
Oba-Shinjo, Sueli Mieko
Camargo, Anamaria Aranha
Moura, Ricardo Pereira
de Aguiar, Paulo Henrique
Cabrera, Hector Navarro
Begnami, Marcos
Rosemberg, Sérgio
Teixeira, Manoel Jacobsen
Marie, Suely Kazue Nagahashi
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
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_short 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
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180167/
https://www.ncbi.nlm.nih.gov/pubmed/22012047
http://dx.doi.org/10.1590/S1807-59322011001000013
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