Inactivation of the DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents Export

@article{citeulike:4908339, abstract = {Background The DNA-repair enzyme O 6-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. 10.1056/NEJM200011093431901}, author = {Esteller, Manel and Garcia-Foncillas, Jesus and Andion, Esther and Goodman, Steven N. and Hidalgo, Oscar F. and Vanaclocha, Vicente and Baylin, Stephen B. and Herman, James G.}, citeulike-article-id = {4908339}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJM200011093431901}, citeulike-linkout-1 = {http://content.nejm.org/cgi/content/abstract/343/19/1350}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11070098}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11070098}, day = {9}, doi = {10.1056/NEJM200011093431901}, journal = {N Engl J Med}, keywords = {agent, alkylating, dna, methylation, mgmt, prognosis, repair}, month = {November}, number = {19}, pages = {1350--1354}, posted-at = {2009-06-19 15:30:55}, priority = {2}, title = {Inactivation of the DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents}, url = {http://dx.doi.org/10.1056/NEJM200011093431901}, volume = {343}, year = {2000} }

TY - JOUR ID - citeulike:4908339 L3 - citeulike-article-id:4908339 N2 - Background The DNA-repair enzyme O 6-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. 10.1056/NEJM200011093431901 IS - 19 JF - N Engl J Med EP - 1354 TI - Inactivation of the DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents VL - 343 SP - 1350 KW - agent KW - alkylating KW - dna KW - methylation KW - mgmt KW - prognosis KW - repair AU - Esteller, Manel AU - Garcia-Foncillas, Jesus AU - Andion, Esther AU - Goodman, Steven AU - Hidalgo, Oscar AU - Vanaclocha, Vicente AU - Baylin, Stephen AU - Herman, James PY - 2000/11/09/ UR - http://dx.doi.org/10.1056/NEJM200011093431901 ER -