MGMT promoter methylation

aka MGMT methylation, MGMT methylated, MGMT promoter methylated, MGMT unmethylated, methylated MGMT, MGMT status

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.

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.

Part ofMGMT (O6-methylguanine-DNA methyltransferase)· MGMT All readouts

MGMT (O6-methylguanine-DNA methyltransferase): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · MGMT is a DNA repair enzyme that removes the damage temozolomide causes; when the gene is switched off by methylation the tumour cannot repair itself and the drug works better.

Methylation No approval threshold

What it means for a patient

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.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

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.

“MGMT promoter methylation status was associated with benefit from temozolomide in the EORTC 26981/22981 NCIC CE.3 trial”
Hegi et al., MGMT gene silencing and benefit from temozolomide in glioblastoma, N Engl J Med 2005

Thresholds used in approvals

No approval uses this readout as a threshold. It is defined by Hegi et al., N Engl J Med 2005 (EORTC 26981/22981 NCIC CE.3 correlative study).

Tests that measure it

Tempus xT and xT CDx Caris MI Profile

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.