MGMT gene silencing and benefit from temozolomide in glioblastoma.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_59DF1F31757A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
MGMT gene silencing and benefit from temozolomide in glioblastoma.
Périodique
New England Journal of Medicine
Auteur(s)
Hegi M.E., Diserens A.C., Gorlia T., Hamou M.F., de Tribolet N., Weller M., Kros J.M., Hainfellner J.A., Mason W., Mariani L., Bromberg J.E., Hau P., Mirimanoff R.O., Cairncross J.G., Janzer R.C., Stupp R.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Statut éditorial
Publié
Date de publication
2005
Volume
352
Numéro
10
Pages
997-1003
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents.
METHODS: We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis.
RESULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups.
CONCLUSIONS: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
Mots-clé
Antineoplastic Agents, Alkylating/therapeutic use, Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Chemotherapy, Adjuvant, DNA Methylation, Dacarbazine/analogs & derivatives, Dacarbazine/therapeutic use, Disease-Free Survival, Gene Silencing, Glioblastoma/drug therapy, Glioblastoma/genetics, Humans, O(6)-Methylguanine-DNA Methyltransferase/genetics, Polymerase Chain Reaction, Promoter Regions, Genetic, Randomized Controlled Trials as Topic, Survival Analysis
Pubmed
Web of science
Création de la notice
28/01/2008 9:39
Dernière modification de la notice
20/08/2019 15:13
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