Cargando…
O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions
Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurre...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397507/ https://www.ncbi.nlm.nih.gov/pubmed/22837675 http://dx.doi.org/10.3390/ijms13066983 |
_version_ | 1782238194271518720 |
---|---|
author | Villalva, Claire Cortes, Ulrich Wager, Michel Tourani, Jean-Marc Rivet, Pierre Marquant, Celine Martin, Sebastien Turhan, Ali G. Karayan-Tapon, Lucie |
author_facet | Villalva, Claire Cortes, Ulrich Wager, Michel Tourani, Jean-Marc Rivet, Pierre Marquant, Celine Martin, Sebastien Turhan, Ali G. Karayan-Tapon, Lucie |
author_sort | Villalva, Claire |
collection | PubMed |
description | Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ. |
format | Online Article Text |
id | pubmed-3397507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-33975072012-07-26 O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions Villalva, Claire Cortes, Ulrich Wager, Michel Tourani, Jean-Marc Rivet, Pierre Marquant, Celine Martin, Sebastien Turhan, Ali G. Karayan-Tapon, Lucie Int J Mol Sci Article Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ. Molecular Diversity Preservation International (MDPI) 2012-06-07 /pmc/articles/PMC3397507/ /pubmed/22837675 http://dx.doi.org/10.3390/ijms13066983 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Villalva, Claire Cortes, Ulrich Wager, Michel Tourani, Jean-Marc Rivet, Pierre Marquant, Celine Martin, Sebastien Turhan, Ali G. Karayan-Tapon, Lucie O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title | O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title_full | O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title_fullStr | O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title_full_unstemmed | O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title_short | O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions |
title_sort | o6-methylguanine-methyltransferase (mgmt) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397507/ https://www.ncbi.nlm.nih.gov/pubmed/22837675 http://dx.doi.org/10.3390/ijms13066983 |
work_keys_str_mv | AT villalvaclaire o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT cortesulrich o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT wagermichel o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT touranijeanmarc o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT rivetpierre o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT marquantceline o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT martinsebastien o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT turhanalig o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions AT karayantaponlucie o6methylguaninemethyltransferasemgmtpromotermethylationstatusingliomastemlikecellsiscorrelatedtotemozolomidesensitivityunderdifferentiationpromotingconditions |