Abstract
Purpose
The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection.
Patients and methods
55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival.
Results
In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021).
Conclusion
We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.
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Acknowledgments
We would like to thank the help given by the Division of Molecular Pathology and Cancer Therapeutics at the Institute of Cancer Research Sutton UK.
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The manuscript has been approved by the responsible authorities of our laboratory and by the ethics committee of Farhat Hached University Hospital of Sousse, Tunisia. We have no substantial direct or indirect commercial or financial incentive associated with publishing this article, and there is no conflict of interest.
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Trabelsi, S., Mama, N., Ladib, M. et al. MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry. Clin Transl Oncol 18, 391–397 (2016). https://doi.org/10.1007/s12094-015-1381-0
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DOI: https://doi.org/10.1007/s12094-015-1381-0