{"entity":{"id":"mgmt-promoter-methylation","kind":"biomarker","name":"MGMT promoter methylation","aka":["MGMT methylation","MGMT methylated","MGMT promoter methylated","MGMT unmethylated","methylated MGMT","MGMT status"],"tldr":"Methylation of the MGMT promoter switches off the repair enzyme that undoes temozolomide's damage. Methylated glioblastomas live longer on temozolomide; unmethylated ones gain little, and trials now use the result to spare or intensify chemotherapy.","summary":"Methylation-specific PCR, pyrosequencing or methylation arrays report the promoter as methylated or unmethylated, with laboratory-specific cut-offs (pyrosequencing commonly 10 percent). The temozolomide (Temodar) label for newly diagnosed glioblastoma does not require MGMT testing; the EORTC/NCIC trial that established the regimen showed the survival benefit concentrated in methylated tumours (Hegi et al., NEJM 2005), and EANO and NCCN guidelines recommend testing, with omission of temozolomide an option for elderly patients with unmethylated tumours. The CeTeG/NOA-09 trial (NCT01149109) tested lomustine plus temozolomide only in methylated glioblastoma.","asOf":"2026-09-23","links":[{"label":"Hegi et al. 2005","url":"https://doi.org/10.1056/NEJMoa043331"},{"label":"TEMODAR prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046a9011-3911-4d3f-a15f-fbb56d5aad56"}],"tags":["biomarker","methylation","no-approval"],"related":["idh1-r132","1p19q-codeletion-readout","h3-k27m"],"cancers":["glioblastoma","idh-mutant-astrocytoma"],"sections":[],"technologies":[],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["mgmt","alkylating-agent"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"mgmt-protein","measurement":"methylation","scoringRule":{"text":"Promoter methylation of MGMT by methylation-specific PCR (methylated versus unmethylated) or pyrosequencing (laboratory cut-off, often around 10 percent mean methylation across CpG sites); no label defines a threshold.","quote":"MGMT promoter methylation status was associated with benefit from temozolomide in the EORTC 26981/22981 NCIC CE.3 trial","source":"https://doi.org/10.1056/NEJMoa043331","sourceLabel":"Hegi et al., MGMT gene silencing and benefit from temozolomide in glioblastoma, N Engl J Med 2005"},"thresholds":[],"definedBy":{"label":"Hegi et al., N Engl J Med 2005 (EORTC 26981/22981 NCIC CE.3 correlative study)","url":"https://doi.org/10.1056/NEJMoa043331"},"tests":["caris-mi-profile","tempus-xt"],"assays":[],"companionDiagnostics":[],"forPatient":"A methylated MGMT result means temozolomide is more likely to help and is a reason to give it in full; an unmethylated result means the benefit is small, and for older patients radiotherapy alone or a trial may be discussed. The result does not change surgery or radiotherapy and is not a drug approval criterion."},"route":"/biomarkers/mgmt-promoter-methylation/","neighbours":{"biomarker":[{"id":"1p19q-codeletion-readout","kind":"biomarker","name":"1p/19q codeletion","route":"/biomarkers/1p19q-codeletion-readout/"},{"id":"h3-k27m","kind":"biomarker","name":"H3 K27M mutation","route":"/biomarkers/h3-k27m/"},{"id":"idh1-r132","kind":"biomarker","name":"IDH1 R132 mutation","route":"/biomarkers/idh1-r132/"}],"cancer":[{"id":"idh-mutant-astrocytoma","kind":"cancer","name":"Astrocytoma, IDH-mutant (grades 2 to 4)","route":"/cancers/idh-mutant-astrocytoma/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"drug":[{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"}],"term":[{"id":"alkylating-agent","kind":"term","name":"Alkylating agents and antimetabolites","route":"/terms/alkylating-agent/"},{"id":"mgmt","kind":"term","name":"MGMT promoter methylation","route":"/terms/mgmt/"}],"target":[{"id":"mgmt-protein","kind":"target","name":"MGMT (O6-methylguanine-DNA methyltransferase)","route":"/targets/mgmt-protein/"}]}}