Titre
Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Hegi, M.E.
Auteure/Auteur
Diserens, A.C.
Auteure/Auteur
Godard, S.
Auteure/Auteur
Dietrich, P.Y.
Auteure/Auteur
Regli, L.
Auteure/Auteur
Ostermann, S.
Auteure/Auteur
Otten, P.
Auteure/Auteur
Van Melle, G.
Auteure/Auteur
de Tribolet, N.
Auteure/Auteur
Stupp, R.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1078-0432
Statut éditorial
Publié
Date de publication
2004
Volume
10
Numéro
6
Première page
1871
Dernière page/numéro d’article
1874
Peer-reviewed
Oui
Langue
anglais
Résumé
PURPOSE: In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy. EXPERIMENTAL DESIGN: The methylation status of MGMT in the tumor biopsies was evaluated in 38 patients undergoing resection for newly diagnosed glioblastoma and enrolled in a Phase II trial testing concomitant and adjuvant temozolomide and radiation. The epigenetic silencing of the MGMT gene was determined using methylation-specific PCR. RESULTS: Inactivation of the MGMT gene by promoter methylation was associated with longer survival (P = 0.0051; Log-rank test). At 18 months, survival was 62% (16 of 26) for patients testing positive for a methylated MGMT promoter but reached only 8% (1 of 12) in absence of methylation (P = 0.002; Fisher's exact test). In the presence of other clinically relevant factors, methylation of the MGMT promoter remains the only significant predictor (P = 0.017; Cox regression). CONCLUSIONS: This prospective clinical trial identifies MGMT-methylation status as an independent predictor for glioblastoma patients treated with a methylating agent. The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.
PID Serval
serval:BIB_C329D5878C62
PMID
Open Access
Oui
Date de création
2008-03-05T14:56:28.362Z
Date de création dans IRIS
2025-05-20T22:46:31Z