Journal
CANCER GENOMICS & PROTEOMICS
Volume 15, Issue 6, Pages 437-446Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/cgp.20102
Keywords
MGMT gene promoter; methylation; pyrosequencing; methylation-specific PCR; glioblastoma; overall survival
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Funding
- Radiumhospitalets Legater
- Larvik kreftforening
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Background: Although methylation of the O-6-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 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. 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. Conclusion: PSQ is the method of choice for MGMT promoter methylation analysis in routine clinical practice.
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