The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/44998 |
Resumo: | Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. |
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The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survivalMalignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.ARC -Fondation ARC pour la Recherche sur le Cancer(EML20120904843)Oxford University Press[et.al.]Universidade do MinhoFogli, AnneChautard, EmmanuelVaurs-Barrière, Catherine Pereira, Bruno Müller-Barthélémy, Mélanie Court, FranckBiau, Julian Pinto, Afonso A.Kémény, Jean-LouisCosta, Bruno Marques20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/44998eng0143-333410.1093/carcin/bgv25126717998http://oxfordjournals.org/info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:47:39Zoai:repositorium.sdum.uminho.pt:1822/44998Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:45:45.675409Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
title |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
spellingShingle |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival Fogli, Anne |
title_short |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
title_full |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
title_fullStr |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
title_full_unstemmed |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
title_sort |
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival |
author |
Fogli, Anne |
author_facet |
Fogli, Anne Chautard, Emmanuel Vaurs-Barrière, Catherine Pereira, Bruno Müller-Barthélémy, Mélanie Court, Franck Biau, Julian Pinto, Afonso A. Kémény, Jean-Louis Costa, Bruno Marques |
author_role |
author |
author2 |
Chautard, Emmanuel Vaurs-Barrière, Catherine Pereira, Bruno Müller-Barthélémy, Mélanie Court, Franck Biau, Julian Pinto, Afonso A. Kémény, Jean-Louis Costa, Bruno Marques |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
[et.al.] Universidade do Minho |
dc.contributor.author.fl_str_mv |
Fogli, Anne Chautard, Emmanuel Vaurs-Barrière, Catherine Pereira, Bruno Müller-Barthélémy, Mélanie Court, Franck Biau, Julian Pinto, Afonso A. Kémény, Jean-Louis Costa, Bruno Marques |
description |
Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/44998 |
url |
http://hdl.handle.net/1822/44998 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0143-3334 10.1093/carcin/bgv251 26717998 http://oxfordjournals.org/ |
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 |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133023228133376 |