Methylguanine-DNA methyltransferase (MGMT)
Updates to Article Attributes
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 tumours with IDH mutations3. In contrast, MGMT methylation is far less common in higher grade gliomas (WHO grade III and IV), found in only 35-45% of such tumours 2.
Assessment
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.
Prognostic impact
High activity of MGMT (i.e. unmethylated) results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor 1,2.
WhenOn the other hand, when the MGMT promoter is methylated, there would be ais 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 protocol2.
-<p><strong>O<sup>6</sup>-Methylguanine-DNA methyltransferase (MGMT)</strong> is a DNA repair enzyme which is important in predicting the effects of alkylating chemotherapeutic agents (e.g. temozolomide) in the treatment of <a href="/articles/glioblastoma">glioblastomas (GBM)</a>. High activity of MGMT results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor <sup>1</sup>. </p><p>When the MGMT promoter is methylated, there would be a decreased activity of MGMT and thus alkylating agents are more effective. In other words, identification of methylated-MGMT is a positive prognostic factor <sup>1</sup>. </p>- +<p><strong>O<sup>6</sup>-Methylguanine-DNA methyltransferase (MGMT)</strong> is a DNA repair enzyme which is important in predicting the effects of alkylating chemotherapeutic agents (e.g. temozolomide) in the treatment of <a href="/articles/glioblastoma">glioblastomas (GBM)</a>.</p><p>MGMT methylation is very common in low-grade gliomas (80%) <sup>2</sup> and is almost invariably present in low-grade tumours with <a href="/articles/isocitrate-dehydrogenase-idh">IDH mutations</a> <sup>3</sup>. In contrast, MGMT methylation is far less common in higher grade gliomas (WHO grade III and IV), found in only 35-45% of such tumours <sup>2</sup>. </p><h4>Assessment</h4><p>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. <a title="Immunohistochemistry" href="/articles/immunohistochemistry">Immunohistochemistry</a>, nonquantitative methylation-specific polymerase chain reaction (MSP) and sequencing have all been used. </p><p>Viable (non-necrotic) tissue must be sampled to avoid false negative results <sup>2</sup>. </p><h4>Prognostic impact</h4><p>High activity of MGMT (i.e. unmethylated) results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor <sup>1,2</sup>. </p><p>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 <sup>1</sup>. It is also predictive of <a title="Tumour pseudoprogression" href="/articles/tumour-pseudoprogression">pseudoprogression</a> following <a title="Stupp protocol for glioblastoma" href="/articles/stupp-protocol-for-glioblastoma">Stupp protocol</a> <sup>2</sup>. </p><p> </p>
References changed:
- 2. Thon N, Kreth S, Kreth FW. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. OncoTargets and therapy. 6: 1363-72. <a href="https://doi.org/10.2147/OTT.S50208">doi:10.2147/OTT.S50208</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/24109190">Pubmed</a> <span class="ref_v4"></span>
- 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. <a href="https://doi.org/10.1002/ijc.26499">doi:10.1002/ijc.26499</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/22020830">Pubmed</a> <span class="ref_v4"></span>
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