Predictive impact of MGMT promoter methylation in glioblastoma of the elderly
Predictive impact of MGMT promoter methylation in glioblastoma of the elderly
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DOI：
10.1002/ijc.27385
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发表时间：
2012-09-15
影响因子：
6.4
通讯作者：
Weller, Michael
中科院分区：
文献类型：
--
作者：
Reifenberger, Guido;Hentschel, Bettina;Weller, Michael
o6 -甲基鸟嘌呤- dna甲基转移酶（MGMT）启动子甲基化鉴定出胶质母细胞瘤患者亚群预后更好，并预测烷基化剂化疗（CT）的益处。其在老年胶质母细胞瘤患者中的患病率及临床意义尚不清楚。我们研究了233名年龄在70岁或以上的胶质母细胞瘤患者（144名男性，89名女性，中位年龄：74岁，范围：70.086.6岁），这些患者被前瞻性地纳入德国胶质瘤网络，通过甲基化特异性PCR （MSP）对所有患者进行MGMT启动子甲基化，并对166名患者进行DNA磷酸测序。MGMT数据与患者预后相关。中位无进展生存期（PFS）为4.8个月（95% CI: 4.35.3），中位总生存期（OS）为7.7个月（95% CI: 6.39.0）。134例（57.5%）患者MSP检测到MGMT启动子甲基化。在整个队列中，MGMT启动子甲基化患者的PFS为5.2个月对4.7个月（p = 0.207）， OS为8.4个月对6.4个月（p = 0.031）。MGMT甲基化肿瘤患者在放疗（RT）加CT或单独CT治疗时，与单独RT治疗的患者相比，PFS更长。MGMT未甲基化肿瘤患者似乎没有从CT中获得生存益处，无论是在诊断时与RT一起给予还是作为补救性治疗。当焦磷酸测序显示出bbbb25 % MGMT甲基化等位基因时，RT + CT或单独CT治疗的患者表现出更长的OS。综上所述，MGMT启动子甲基化可能是一种有用的生物标志物，可以对老年胶质母细胞瘤患者进行分层，以选择是否使用烷基化剂CT治疗。
O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.086.6 years), who were prospectively enrolled in the German Glioma Network, for MGMT promoter methylation by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were correlated with patient outcome. Median progression-free survival (PFS) was 4.8 months (95% CI: 4.35.3) and median overall survival (OS) was 7.7 months (95% CI: 6.39.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4 versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter methylation. Patients with MGMT methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with MGMT unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT.