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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.
MGMT is a suicide enzyme that transfers alkyl groups off the O6 position of guanine onto itself, reversing the lesion that temozolomide and nitrosoureas rely on. Promoter methylation silences the gene in about 40 percent of glioblastomas and predicts longer survival with temozolomide; the readout page under this target carries the test methods and the trials that use methylation to select or spare chemotherapy.
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.
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.
Loss of MGMT leaves O6-methylguanine unrepaired, which mispairs with thymine and triggers mismatch-repair-driven cell death; tumours that lose mismatch repair as well become hypermutated and resistant.
No product in this corpus aims at MGMT (O6-methylguanine-DNA methyltransferase) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Tumour-associated overexpression: HPA finds the RNA tissue enhanced in normal liver, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA MGMT: RNA tissue enhanced (liver 126 nTPM); high antibody staining in 30 normal tissues; highest cancer staining renal cancer (6 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Brain and spinal cord tumours (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas MGMT tissue; Human Protein Atlas MGMT pathology; Open Targets ENSG00000170430 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Tano et al, Proc. Natl. Acad. Sci. U.S.A, 1990, "Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Loss of MGMT leaves O6-methylguanine unrepaired, which mispairs with thymine and triggers mismatch-repair-driven cell death; tumours that lose mismatch repair as well become hypermutated and resistant.
RNA: tissue enhanced (liver 126 nTPM), detected in all normal tissues.
Medium: Adrenal gland, Bone marrow, Caudate, Cerebral cortex, Esophagus, Gallbladder, Hippocampus, Oral mucosa.
Medium only: breast cancer, carcinoid, colorectal cancer, endometrial cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query for this target: (TITLE:"MGMT" OR ABSTRACT:"MGMT" OR TITLE:"O6-methylguanine-DNA methyltransferase" OR ABSTRACT:"O6-methylguanine-DNA methyltransferase" OR TITLE:"O-6-methylguanine-DNA methyltransferase" OR ABSTRACT:"O-6-methylguanine-DNA methyltransferase" OR TITLE:"AGT" OR ABSTRACT:"AGT" OR TITLE:"O6-alkylguanine DNA alkyltransferase" OR ABSTRACT:"O6-alkylguanine DNA alkyltransferase") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MGMT (O6-methylguanine-DNA methyltransferase), not a curated reading list.
Shares CIViC and the tag biomarker-parent.
Shares CIViC and the tag biomarker-parent.
Shares CIViC and the tag biomarker-parent.
Shares Glioma & glioblastoma, CIViC and the tag biomarker-parent.
Shares Temozolomide, Glioma & glioblastoma.
Shares Temozolomide, Glioma & glioblastoma.
Shares Temozolomide, Glioma & glioblastoma.
Shares Temozolomide, Glioma & glioblastoma.