Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents - PubMed (original) (raw)
. 2000 Nov 9;343(19):1350-4.
doi: 10.1056/NEJM200011093431901.
Affiliations
- PMID: 11070098
- DOI: 10.1056/NEJM200011093431901
Free article
Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents
M Esteller et al. N Engl J Med. 2000.
Free article
Erratum in
- N Engl J Med 2000 Dec 7;343(23):1740
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.
Comment in
- Pharmacogenomics--teaching old drugs new tricks.
Weinstein JN. Weinstein JN. N Engl J Med. 2000 Nov 9;343(19):1408-9. doi: 10.1056/NEJM200011093431910. N Engl J Med. 2000. PMID: 11070107 No abstract available. - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.
Buckner JC, Moynihan TJ. Buckner JC, et al. N Engl J Med. 2001 Mar 1;344(9):686; author reply 687-8. N Engl J Med. 2001. PMID: 11229337 No abstract available. - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.
Quinn DI. Quinn DI. N Engl J Med. 2001 Mar 1;344(9):686; author reply 687-8. N Engl J Med. 2001. PMID: 11229338 No abstract available. - The DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.
Ali-Osman F, Srivenugopal K, Sawaya R. Ali-Osman F, et al. N Engl J Med. 2001 Mar 1;344(9):687; author reply 687-8. N Engl J Med. 2001. PMID: 11229339 No abstract available.
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