摘要
BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt 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 radioth erapy (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 sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt 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 radioth erapy (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 sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
出处
《世界核心医学期刊文摘（神经病学分册）》
2005年第9期7-8,共2页
Digest of the World Core Medical Journals:Clinical Neurology
