O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme which is important in predicting the effects of alkylating chemotherapeutic agents (e.g. temozolomide) in the treatment of glioblastomas (GBM).
MGMT methylation is very common in low-grade gliomas (80%) 2 and is almost invariably present in low-grade tumors with IDH mutations 3. In contrast, MGMT methylation is far less common in higher grade gliomas (WHO grade III and IV), found in only 35-45% of such tumors 2.
MGMT methylation can be assessed with numerous techniques and no uniform consensus has been reached in regards to which technique is the most appropriate in clinical practice. Immunohistochemistry, nonquantitative methylation-specific polymerase chain reaction (MSP) and sequencing have all been used.
Viable (non-necrotic) tissue must be sampled to avoid false negative results 2.
High activity of MGMT (i.e. unmethylated) results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor 1,2.
On the other hand, when the MGMT promoter is methylated, there is decreased activity of MGMT and thus alkylating agents are more effective. In other words, identification of methylated-MGMT is a positive prognostic factor 1. It is also predictive of pseudoprogression following Stupp protocol 2.
- 1. Weller M, Stupp R, Reifenberger G et-al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine?. Nat Rev Neurol. 2009;6 (1): 39-51. doi:10.1038/nrneurol.2009.197 - Pubmed citation
- 2. Thon N, Kreth S, Kreth FW. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. OncoTargets and therapy. 6: 1363-72. doi:10.2147/OTT.S50208 - Pubmed
- 3. Mulholland S, Pearson DM, Hamoudi RA, Malley DS, Smith CM, Weaver JM, Jones DT, Kocialkowski S, Bäcklund LM, Collins VP, Ichimura K. MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations. International journal of cancer. 131 (5): 1104-13. doi:10.1002/ijc.26499 - Pubmed
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