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Cancer Genomics Proteomics. 2018 Nov-Dec;15(6):437-446. doi: 10.21873/cgp.20102.

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

Author information

1
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
2
Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
3
Department of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway.
4
Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
5
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
6
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway ioannis.panagopoulos@rr-research.no.

Abstract

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 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.

KEYWORDS:

MGMT gene promoter; glioblastoma; methylation; methylation-specific PCR; overall survival; pyrosequencing

PMID:
30343277
DOI:
10.21873/cgp.20102

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