Methylguanine-DNA Methyltransferase (MGMT)

O-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%)  and is almost invariably present in low-grade tumors with IDH mutations . 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 .


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 .

Prognostic impact

High activity of MGMT (i.e. unmethylated) results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor .

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 . It is also predictive of pseudoprogression following Stupp protocol .

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