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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2011
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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. |
format | Online Article Text |
id | pubmed-3180167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo |
record_format | MEDLINE/PubMed |
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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