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Changes of O6-Methylguanine DNA Methyltransferase (MGMT) Promoter Methylation in Glioblastoma Relapse—A Meta-Analysis Type Literature Review

1
Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany
2
Department of Neuropathology, Institute of Pathology, University of Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(12), 1837; https://doi.org/10.3390/cancers11121837
Received: 7 October 2019 / Revised: 11 November 2019 / Accepted: 19 November 2019 / Published: 21 November 2019
(This article belongs to the Special Issue Tumors of the Central Nervous System: An Update)
Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24%; CI: 0.21–0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic. View Full-Text
Keywords: glioblastoma multiforme (GBM); glioma; relapse; temozolomide; MGMT promoter methylation; therapy; resistance; recurrence glioblastoma multiforme (GBM); glioma; relapse; temozolomide; MGMT promoter methylation; therapy; resistance; recurrence
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Feldheim, J.; Kessler, A.F.; Monoranu, C.M.; Ernestus, R.-I.; Löhr, M.; Hagemann, C. Changes of O6-Methylguanine DNA Methyltransferase (MGMT) Promoter Methylation in Glioblastoma Relapse—A Meta-Analysis Type Literature Review. Cancers 2019, 11, 1837.

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