Esteller M, Garcia-Foncillas J, Andion E, Goodman S N, Hidalgo O F, Vanaclocha V, Baylin S B, Herman J G
Division of Cancer Biology, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
N Engl J Med. 2000 Nov 9;343(19):1350-4. doi: 10.1056/NEJM200011093431901.
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.
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.
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.
Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.
DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）可抑制烷化剂对肿瘤细胞的杀伤作用。MGMT的活性受启动子调控；启动子甲基化会使该基因在癌症中沉默，细胞不再产生MGMT。我们研究了胶质瘤，以确定MGMT启动子甲基化是否与肿瘤对烷化剂的反应性相关。
我们采用甲基化特异性聚合酶链反应分析法分析肿瘤DNA中的MGMT启动子。这些胶质瘤取自接受卡莫司汀（1,3-双（2-氯乙基）-1-亚硝基脲，即BCNU）治疗的患者。将分子数据与临床结果相关联。
47例患者中有19例（40%）的胶质瘤中MGMT启动子发生甲基化。这一发现与肿瘤消退以及总生存期和无病生存期延长相关。它是一个独立且比年龄、分期、肿瘤分级或体能状态更强的预后因素。
胶质瘤中MGMT启动子甲基化是肿瘤对烷化剂反应性的一个有用预测指标。
