Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/176306
Title: Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents
Author: Esteller, Manel
Garcia-Foncillas, Jesús
Andion, Esther
Goodman, Steve N.
Hidalgo, Oscar F.
Vanaclocha, Vicente
Herman, J.G.
Keywords: Ús terapèutic
Tumors cerebrals
Enzimologia
ADN
Genètica
Glioma
Therapeutic use
Brain tumors
Enzymology
DNA
Genetics
Gliomas
Issue Date: 9-Nov-2000
Publisher: Massachusetts Medical Society
Abstract: Background: the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. Methods: we analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. Results: the MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. Conclusions: methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.
Note: Reproducció del document publicat a: https://doi.org/10.1056/NEJM200011093431901
It is part of: New England Journal of Medicine, 2000, vol. 343, num. 19, p. 1350-1354
URI: http://hdl.handle.net/2445/176306
Related resource: https://doi.org/10.1056/NEJM200011093431901
ISSN: 0028-4793
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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