MGMT Gene Promoter Methylation Status - Assessment of Two Pyrosequencing Kits and Three Methylation-specific PCR Methods for their Predictive Capacity in Glioblastomas

MGMT 基因启动子甲基化状态 - 评估两种焦磷酸测序试剂盒和三种甲基化特异性 PCR 方法对胶质母细胞瘤的预测能力

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作者:Lene E Johannessen, Petter Brandal, Tor Åge Myklebust, Sverre Heim, Francesca Micci, Ioannis Panagopoulos

Background

Although methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection. Materials and

Conclusion

PSQ is the method of choice for MGMT promoter methylation analysis in routine clinical practice.

Methods

Methylation of MGMT promoter was examined by methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP, methylation-sensitive high-resolution melting analysis, and two commercial pyrosequencing (PSQ) kits. Survival was compared among 48 patients with glioblastoma according to assay

Results

Only PSQ and MSP significantly separated patients who benefited from temozolomide, with PSQ being the superior method. For PSQ analysis, the cut-off value that best correlated with prognostic outcome was 7% methylation of MGMT. Median survival in patients with MGMT promoter methylation above this cut-off value was 7.8 months longer compared to those with less than 7% methylation. Two-year overall survival for the two groups was 42% and 7.4%, respectively.

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