Affinage

MGMT

Methylated-DNA--protein-cysteine methyltransferase · UniProt P16455

Length
207 aa
Mass
21.6 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MGMT is a suicide DNA repair alkyltransferase that directly reverses alkylation damage by irreversibly transferring the alkyl group from the O6 position of guanine to its own active-site cysteine (Cys145), inactivating itself in the process and also handling larger O6 adducts such as O6-chloroethylguanine (PMID:17485253, PMID:11981013, PMID:17482889). Its central biological importance lies in determining cytotoxic outcome of alkylating agents: unrepaired O6-methylguanine is the dominant genotoxic, recombinogenic and apoptotic lesion, and its killing requires MutS-alpha-dependent mismatch repair and extensive replication, generating secondary double-strand breaks that activate an ATM/ATR→Chk1/Chk2→p53/p73 apoptotic cascade (PMID:17485253, PMID:11554312). This mechanism makes MGMT status the principal determinant of temozolomide response, and epigenetic silencing of MGMT by promoter CpG-island methylation—linked to a non-permissive chromatin state and loss of transcript and enzymatic activity—predicts clinical benefit from temozolomide in glioblastoma (PMID:15758010, PMID:21097691). MGMT abundance is controlled at multiple additional layers: transcriptionally through a Gli1 binding site, an intergenic MKI67–MGMT enhancer, BRD4/Pol II occupancy, and HDAC2–DMAP1–mediated histone deacetylation antagonized by Fstl1–DIP2A (PMID:29225516, PMID:30054476, PMID:36513631, PMID:30542120); through gene-body cytosine modification and genomic rearrangements that drive overexpression independent of promoter methylation (PMID:24568970, PMID:32753598); and post-translationally via NDRG1 binding and stabilization and HDAC8–ADRM1 control of protein turnover (PMID:24367102, PMID:31798765). MGMT also engages in functional crosstalk with base-excision repair through direct DNA-independent interaction with PARP1, which PARylates MGMT to enhance O6-methylguanine repair (PMID:36242092). Beyond repair, MGMT exerts a non-canonical pro-survival role by transcriptionally activating DUB3 to stabilize the anti-apoptotic protein MCL1, promoting chemoresistance (PMID:30718431), and a CHK1–DDX46–LINC01956 axis remodels MGMT mRNA to promote its nuclear export and protein accumulation under temozolomide stress (PMID:39356744).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 High

    Established the core catalytic mechanism: how MGMT removes mutagenic O6-alkyl lesions, defining it as a single-turnover suicide enzyme.

    Evidence In vitro biochemical and active-site characterization showing irreversible alkyl transfer to Cys145

    PMID:11981013 PMID:17482889 PMID:17485253

    Open questions at the time
    • Does not address how spent MGMT is degraded or recycled in vivo
    • No structural detail on substrate selectivity for larger adducts
  2. 2007 High

    Resolved why MGMT loss is cytotoxic by placing unrepaired O6-methylguanine downstream of mismatch repair and within an ATM/ATR→Chk→p53/p73 apoptotic cascade.

    Evidence Genetic epistasis in MGMT-modulated and MMR-deficient cells with apoptosis pathway analysis

    PMID:11554312 PMID:17485253

    Open questions at the time
    • Exact molecular trigger converting O6-MeG mispairs to double-strand breaks not fully defined
    • Relative contribution of p53 vs p73 unresolved
  3. 2001 High

    Defined the lesion hierarchy dictated by MGMT level, showing O6-MeG dominates genotoxicity in MGMT-deficient cells while BER-repaired N-alkylations dominate when MGMT is high.

    Evidence Gain/loss-of-function modulation of MGMT and BER components with survival readouts

    PMID:11554312

    Open questions at the time
    • Quantitative thresholds of MGMT activity setting the switch not established
  4. 2005 High

    Connected MGMT promoter CpG methylation to gene silencing and to clinical temozolomide benefit, making MGMT status a predictive biomarker.

    Evidence Methylation-specific PCR on randomized-trial glioblastoma tissue correlated with survival

    PMID:15758010

    Open questions at the time
    • Does not explain methylation-independent silencing or reactivation
    • Assay does not measure enzymatic activity directly
  5. 2010 High

    Confirmed that promoter methylation translates into functional loss by linking non-permissive chromatin to undetectable transcript and enzymatic activity.

    Evidence Chromatin, RT-PCR and activity assays in paired glioblastoma and sphere samples; H3K9 dimethylation and methyl-CpG binding marks defined in silenced cells

    PMID:16094446 PMID:21097691

    Open questions at the time
    • Mechanism establishing the silenced chromatin state not defined
    • Methylation-independent silencing in some cells unexplained
  6. 2013 High

    Identified post-translational stabilization as a resistance mechanism, showing NDRG1 binds and stabilizes MGMT protein independent of transcription.

    Evidence Reciprocal Co-IP, knockdown/overexpression and in vivo tumor models

    PMID:24367102

    Open questions at the time
    • Structural basis of NDRG1-MGMT binding unknown
    • Whether NDRG1 blocks specific degradation pathway not defined
  7. 2017 Medium

    Revealed methylation-independent transcriptional control by mapping a direct Gli1 binding site upstream of the MGMT start site.

    Evidence ChIP, Gli1 gain/loss-of-function and xenograft validation

    PMID:29225516

    Open questions at the time
    • Single lab; cooperating transcription factors at the promoter not mapped
  8. 2018 High

    Demonstrated distal and chromatin-level transcriptional regulation through an intergenic MKI67-MGMT enhancer and Fstl1-DIP2A-controlled histone acetylation.

    Evidence CRISPR enhancer deletion/activation and reciprocal Co-IP/ChIP for the Fstl1-DIP2A-HDAC2-DMAP1 axis in PDX and resistant models

    PMID:30054476 PMID:30542120

    Open questions at the time
    • Interplay between enhancer activity and promoter methylation not resolved
    • Upstream signals controlling Fstl1/DIP2A nuclear shuttling unclear
  9. 2014 Medium

    Showed gene-body methylation positively regulates MGMT, distinguishing it from repressive promoter methylation and providing a decitabine-sensitive node.

    Evidence Methylation profiling of 91 tumors plus decitabine intervention with expression and TMZ readouts

    PMID:24568970

    Open questions at the time
    • Reader/effector linking gene-body methylation to transcription not identified
  10. 2019 High

    Uncovered a CHK1-engaging therapeutic vulnerability and a non-canonical pro-survival output, with MGMT-deficient cells sensitized to ATR inhibition and MGMT activating a DUB3-MCL1 anti-apoptotic axis.

    Evidence ATR/Chk1 damage and inhibitor combination studies; Co-IP and transcriptional reporter assays for the MGMT-DUB3-MCL1 axis with in vivo validation

    PMID:30718431 PMID:31273061

    Open questions at the time
    • How MGMT transcriptionally activates DUB3 mechanistically undefined
    • DUB3-MCL1 axis tested mainly in ovarian cancer context
  11. 2019 Medium

    Extended protein-level control by linking HDAC8-ADRM1 to MGMT turnover, providing a methylation-independent way to deplete MGMT pharmacologically.

    Evidence HDAC8 inhibition/shRNA and HDAC8-ADRM1 Co-IP with MGMT and viability readouts

    PMID:31798765

    Open questions at the time
    • Single lab; whether HDAC8 acts via deacetylation or scaffolding of ADRM1 unresolved
  12. 2022 High

    Established direct repair-pathway crosstalk by demonstrating PARP1 binds and PARylates MGMT to enhance O6-MeG repair, and that MGMT-positive cells depend on PARP under temozolomide.

    Evidence Co-IP, in vitro PARylation and chromatin-binding assays; MGMT-stratified PARP inhibitor combination studies in vitro and in vivo

    PMID:25777962 PMID:36242092

    Open questions at the time
    • PARylation site(s) on MGMT and effect on its suicide mechanism not mapped
  13. 2024 High

    Defined post-transcriptional and chronobiological control of MGMT, with a CHK1-DDX46-LINC01956 axis driving MGMT mRNA export and intrinsic circadian rhythms in MGMT activity dictating temozolomide timing sensitivity.

    Evidence RIP/CLIP, mRNA export assays and CHK1 inhibitor rescue in PDX/organoids; circadian bioluminescence reporters with timed TMZ dosing and O6-benzylguanine rescue

    PMID:38277015 PMID:39356744

    Open questions at the time
    • Generality of the LINC01956 mechanism beyond methylated glioblastoma untested
    • Clock components directly driving MGMT promoter rhythmicity not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse transcriptional, post-transcriptional and post-translational regulators of MGMT are integrated into a unified control logic, and whether MGMT's non-repair functions are broadly operative, remains unresolved.
  • No structural model of regulated MGMT complexes
  • Cross-regulation among NDRG1, PARP1, HDAC8 and the LINC01956 axis untested
  • Physiological (non-cancer) role of MGMT regulation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 2 GO:0140097 catalytic activity, acting on DNA 2 GO:0016740 transferase activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ADRM1DDX46NDRG1PARP1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 MGMT is a suicide enzyme (alkyltransferase) that repairs O6-alkylguanine DNA lesions by irreversibly transferring the alkyl group from the O6 position of guanine to a cysteine residue in its own active site (Cys145), thereby becoming inactivated in the process. It also repairs larger adducts at the O6-position such as O6-chloroethylguanine. In vitro biochemical assays, active-site characterization, review of mechanistic studies DNA repair High 11981013 17482889 17485253
2007 O6-methylguanine (O6-MeG) induced by MGMT-repaired lesions causes cell death and clastogenicity via a mechanism that requires MutS-alpha-dependent mismatch repair (MMR), whereas O6-chloroethylguanine-induced killing occurs independently of MMR. Extensive DNA replication is required for O6-MeG to provoke cytotoxicity, and the secondary DNA double-strand breaks trigger apoptosis via ATM/ATR, Chk1, Chk2, p53, and p73. Genetic epistasis using MGMT-modulated and MMR-deficient cell systems; apoptosis pathway analysis DNA repair High 11554312 17485253
2001 In MGMT-deficient cells, O6-methylguanine is the major genotoxic, recombinogenic, and apoptotic lesion; its cytotoxicity requires mismatch repair. In cells with high MGMT expression or low O6-methylguanine formation, N-alkylation lesions repaired by base excision repair (BER) become the dominant genotoxic lesions. Genetic modulation (transfection, mutational inactivation) of MGMT and BER components; cell survival assays Progress in nucleic acid research and molecular biology High 11554312
2005 Epigenetic silencing of MGMT by promoter CpG island methylation suppresses MGMT expression in glioblastoma, and this silencing predicts benefit from temozolomide chemotherapy. Promoter methylation was confirmed as the key mechanism of MGMT gene silencing. Methylation-specific PCR of tumor tissue from a randomized clinical trial; correlation with survival outcomes The New England journal of medicine High 15758010
2005 Dimethylation of histone H3 lysine 9 and binding of methyl-CpG binding proteins are common and essential epigenetic marks in MGMT-silenced cancer cells, and MGMT silencing can occur without DNA hypermethylation in some cancer cells. Chromatin immunoprecipitation and analysis of histone modifications in MGMT-silenced cell lines Biochemistry and cell biology Medium 16094446
2010 In MGMT-methylated glioblastoma, MGMT promoter methylation correlates with a non-permissive chromatin status, very low MGMT transcript levels, and undetectable MGMT enzymatic activity, demonstrating functional linkage between epigenetic silencing and loss of repair capacity. Chromatin status analysis, real-time PCR for MGMT transcript, MGMT activity assay in paired glioblastoma and glioblastoma-derived sphere samples Clinical cancer research High 21097691
2013 NDRG1 (an mTOR target induced by hypoxia, irradiation, corticosteroids, and chronic alkylating agent exposure) binds and stabilizes MGMT protein, thereby conferring MGMT-dependent resistance to alkylating chemotherapy in glioblastoma. Co-immunoprecipitation, Western blot, NDRG1 knockdown/overexpression, in vivo tumor models Proceedings of the National Academy of Sciences of the United States of America High 24367102
2019 In MGMT-deficient tumor cells, temozolomide activates the ATR-Chk1 signaling axis (inducing DNA double-strand breaks and G2-M arrest leading to ATR-dependent Chk1 phosphorylation) in an MGMT-status-dependent manner, and this sensitizes MGMT-deficient cells to ATR inhibitors both in vitro and in vivo. Cell viability assays, DNA damage markers (γ-H2AX), cell cycle analysis, ATR inhibitor combination in vitro and in vivo across multiple tumor cell types Cancer research High 31273061
2022 PARP1 and MGMT interact directly in a DNA-independent manner; upon DNA damage, PARP1 PARylates MGMT, and this PARylation enhances O6-methylguanine repair, revealing functional crosstalk between BER (PARP1) and MGMT-mediated direct reversal repair pathways. Co-immunoprecipitation, in vitro PARylation assay, DNA damage-inducible complex formation, chromatin binding assays Journal of hematology & oncology High 36242092
2016 Post-translational modifications of MGMT including ubiquitination, sumoylation, and glutathionylation affect MGMT protein stability and DNA repair activity. The active site Cys145 can be targeted by thiol-reacting compounds (e.g., disulfiram, dithiocarbamates) to inactivate and deplete MGMT. Biochemical assays of PTM effects on MGMT stability and activity; active-site mutagenesis and chemical inhibition studies Mini reviews in medicinal chemistry Medium 26202203
2019 MGMT activates DUB3 transcription, and the resulting MGMT-DUB3-MCL1 axis promotes chemoresistance in ovarian cancer: DUB3 interacts with and deubiquitinates MCL1 in the cytoplasm, protecting MCL1 from proteasomal degradation. Co-immunoprecipitation (DUB3-MCL1 interaction), transcriptional reporter assays (MGMT activating DUB3), in vitro and in vivo functional studies with MGMT inhibitor PaTrin-2 Proceedings of the National Academy of Sciences of the United States of America Medium 30718431
2018 An enhancer located between the MKI67 and MGMT gene promoters is activated in temozolomide-resistant glioblastoma; forced activation of this enhancer increases MGMT expression, and CRISPR/Cas9-mediated deletion of the enhancer reduces MGMT expression and restores temozolomide sensitivity. CRISPR/Cas9 enhancer deletion and activation, gene expression analysis, TMZ sensitivity assays in patient-derived xenograft lines and recurrent tumor samples Nature communications High 30054476
2019 NF-κB signaling regulates MGMT expression: NF-κB inhibition by MG-132 decreases MGMT expression in glioma stem-like cells and enhances temozolomide sensitivity in MGMT-positive GSCs. NF-κB inhibitor (MG-132) treatment, Western blot for MGMT, cell viability/IC50 assays in glioma stem-like cells Chinese journal of cancer Low 23958055
2017 Hedgehog/Gli1 signaling pathway regulates MGMT expression independently of MGMT promoter methylation. Gli1 binds a site at -411 to -403 bp upstream of the MGMT transcriptional start site, and activation or inhibition of Gli1 increases or decreases MGMT expression and TMZ resistance respectively. Chromatin immunoprecipitation identifying Gli1 binding site in MGMT promoter, Gli1 overexpression/inhibition (cyclopamine), methylation-specific PCR, in vivo xenograft model Cancer cell international Medium 29225516
2018 Fstl1 regulates MGMT expression via the DIP2A/HDAC2-DMAP1 axis: DIP2A cooperates with the HDAC2-DMAP1 complex to enhance H3K9Ac deacetylation at the MGMT promoter and suppress MGMT transcription. Fstl1 competitively binds DIP2A to block its nuclear translocation, preventing DIP2A from binding the HDAC2-DMAP1 complex and resulting in increased H3K9Ac and MGMT expression. Co-immunoprecipitation (Fstl1-DIP2A, DIP2A-HDAC2-DMAP1), nuclear fractionation, ChIP (H3K9Ac at MGMT promoter), knockdown/overexpression, in vivo and in vitro TMZ resistance assays Oncogene High 30542120
2019 HDAC8 regulates MGMT protein levels via interaction with the proteasome receptor ADRM1. HDAC8 inhibition decreases MGMT protein levels in glioblastoma cell lines independently of MGMT promoter methylation status; this interaction between HDAC8 and ADRM1 is disrupted by temozolomide exclusively in TMZ-sensitive cells. HDAC8-specific inhibitor and shRNA knockdown, ADRM1 interaction studies (Co-IP), Western blot for MGMT, cell viability assays Genes & cancer Medium 31798765
2022 BET protein inhibition (BETi) reduces MGMT expression in glioblastoma cells by reducing BRD4 and RNA polymerase II binding at the MGMT promoter. BETi also inhibits temozolomide-induced MGMT upregulation; ectopic MGMT expression under an unrelated promoter is unaffected by BETi, confirming the mechanism is transcriptional and promoter-specific. ChIP for BRD4 and Pol II at MGMT promoter, ectopic MGMT overexpression controls, γ-H2AX assay, BETi treatment in glioblastoma-derived spheres Cell death & disease High 36513631
2020 MGMT genomic rearrangements (structural variants) in recurrent gliomas lead to MGMT overexpression independently of promoter methylation changes; CRISPR/Cas9-generated MGMT rearrangements in glioma cells confer temozolomide resistance both in vitro and in vivo. CRISPR/Cas9-mediated genomic rearrangements, gene expression analysis, in vitro and in vivo TMZ resistance assays, exosome detection of fusion transcripts Nature communications High 32753598
2014 Gene body cytosine modifications in the MGMT locus positively regulate MGMT expression independently of promoter methylation; inducing gene body hypomethylation with decitabine decreases MGMT expression in glioblastoma and lymphoblastoid cell lines and sensitizes resistant cells to temozolomide. Methylation analysis of 91 glioblastoma samples, decitabine treatment with MGMT expression measurement, TMZ sensitivity assays Molecular cancer therapeutics Medium 24568970
2020 MGMT suppresses ATG4B expression in gastric cancer cells, thereby inhibiting autophagy; cisplatin inhibits MGMT, which leads to ATG4B upregulation, increased autophagy, and decreased chemosensitivity. MGMT inhibition-mediated ATG4B derepression drives autophagy-dependent DDP resistance. MGMT knockdown/inhibition, ATG4B expression analysis, autophagy assays, in vivo xenograft model with chloroquine combination Biomedicine & pharmacotherapy Low 32007918
2024 In MGMT-methylated glioblastoma cells, temozolomide activates CHK1, which phosphorylates the RNA helicase DDX46, inducing a dense-to-loose conformational change that increases DDX46 helicase activity. DDX46-mediated structural remodeling of lncRNA LINC01956 exposes binding motifs that interact with the 3'UTR of MGMT mRNA, promoting nuclear export and increased MGMT protein abundance, thus driving TMZ resistance. RNA immunoprecipitation (RIP), CLIP, structural analysis, mRNA export assays, PDX and tumor organoid models, CHK1 inhibitor rescue experiments Science translational medicine High 39356744
2024 MGMT expression and promoter methylation exhibit intrinsic circadian rhythms in glioblastoma cells; MGMT activity is lowest at the daily peak of Bmal1 transcription, and TMZ sensitivity correspondingly peaks at this time. Inhibition of MGMT activity with O6-benzylguanine abolishes the daily rhythm in TMZ sensitivity. Real-time bioluminescence reporters for circadian clock genes and MGMT, MGMT transcript and methylation time-course analysis, TMZ viability assays at different circadian times, in vivo xenograft morning vs. evening TMZ delivery Journal of neuro-oncology Medium 38277015
2015 MGMT-positive cancer cells show strong dependence on PARP for survival under temozolomide treatment; in vitro and in vivo, MGMT-positive (but not MGMT-deficient) cells are highly sensitive to the combination of temozolomide and PARP inhibitors, with MGMT-positive melanoma cells undergoing enhanced senescence. In vitro cell viability assays, in vivo tumor models, PARP inhibitor combination studies stratified by MGMT expression Molecular cancer therapeutics Medium 25777962
2007 MGMT polymorphic variants Leu84Phe, Ile143Val, and Lys178Arg have subtle effects on alkyltransferase activity; studies in cells show these variants do not dramatically alter repair function. The proposed role of alkylated MGMT in modifying Estrogen Receptor alpha activity was not confirmed as a major function in experimental studies. Alkyltransferase activity assays of polymorphic variants, ER-alpha transcriptional reporter assays DNA repair Medium 17569599
2012 A high-throughput MGMT activity assay was developed based on the mechanism whereby MGMT irreversibly transfers the alkyl group from O6-position guanine to its active site cysteine; biotin-tagged O6-benzylguanine (a substrate analog) is transferred to MGMT, forming a MGMT-BG-biotin complex that can be captured on anti-MGMT-coated plates and quantified. Biochemical assay development using MGMT's suicide mechanism; validation in cell extracts with streptavidin-alkaline phosphatase detection Mutation research Medium 22609488
2019 IKBKE enhances temozolomide resistance in glioblastoma cells by activating the AKT/NF-κB signaling pathway, which upregulates MGMT expression; IKBKE knockdown reduces MGMT levels and sensitizes cells to TMZ in vitro and in vivo. IKBKE knockdown/overexpression, Western blot for MGMT and AKT/NF-κB pathway components, cell proliferation and apoptosis assays, in vivo intracranial xenograft model Clinical & translational oncology Low 31865606

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 MGMT gene silencing and benefit from temozolomide in glioblastoma. The New England journal of medicine 5719 15758010
2008 Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 681 18757334
2009 MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nature reviews. Neurology 603 19997073
2007 MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA repair 506 17485253
2014 MGMT testing--the challenges for biomarker-based glioma treatment. Nature reviews. Neurology 432 24912512
2005 MGMT promoter methylation and field defect in sporadic colorectal cancer. Journal of the National Cancer Institute 390 16174854
2002 Clinical relevance of MGMT in the treatment of cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 362 11981013
2020 MGMT Status as a Clinical Biomarker in Glioblastoma. Trends in cancer 257 32348734
2005 Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. International journal of cancer 234 15455350
2018 A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma. Nature communications 211 30054476
2020 O6-Methylguanine-DNA Methyltransferase (MGMT): Challenges and New Opportunities in Glioma Chemotherapy. Frontiers in oncology 205 32010632
2006 Targeted modulation of MGMT: clinical implications. Clinical cancer research : an official journal of the American Association for Cancer Research 195 16428468
2011 O(6)-Methylguanine-DNA methyltransferase (MGMT) in normal tissues and tumors: enzyme activity, promoter methylation and immunohistochemistry. Biochimica et biophysica acta 193 21745538
2015 Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression. PloS one 156 26447477
2020 MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nature communications 154 32753598
2013 mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy. Proceedings of the National Academy of Sciences of the United States of America 154 24367102
2015 IDH mutation and MGMT promoter methylation in glioblastoma: results of a prospective registry. Oncotarget 125 26503470
2013 Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. OncoTargets and therapy 123 24109190
2011 O-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation. PloS one 99 21365007
2008 MGMT immunohistochemical expression and promoter methylation in human glioblastoma. Applied immunohistochemistry & molecular morphology : AIMM 96 18091318
2008 Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study. Neuroepidemiology 93 18997474
2016 MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors. Endocrine-related cancer 92 27353036
2001 BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis. Progress in nucleic acid research and molecular biology 80 11554312
2010 MGMT modulates glioblastoma angiogenesis and response to the tyrosine kinase inhibitor sunitinib. Neuro-oncology 75 20179017
2019 MGMT-activated DUB3 stabilizes MCL1 and drives chemoresistance in ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America 71 30718431
2005 Epigenetic silencing of the MGMT gene in cancer. Biochemistry and cell biology = Biochimie et biologie cellulaire 71 16094446
2013 Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells. Chinese journal of cancer 70 23958055
2010 Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres. Clinical cancer research : an official journal of the American Association for Cancer Research 67 21097691
2012 Volumetric and MGMT parameters in glioblastoma patients: survival analysis. BMC cancer 65 22214427
2010 MGMT promoter methylation in malignant gliomas. Targeted oncology 62 20725792
2006 Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Current opinion in pharmacology 62 16777483
2007 DNA repair polymorphisms XRCC1 and MGMT and risk of adult gliomas. Neuroepidemiology 60 17898525
2008 Polymorphisms in MGMT and DNA repair genes and the risk of esophageal adenocarcinoma. International journal of cancer 57 18386788
2019 Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer research 52 31273061
2019 Changes of O6-Methylguanine DNA Methyltransferase (MGMT) Promoter Methylation in Glioblastoma Relapse-A Meta-Analysis Type Literature Review. Cancers 52 31766430
2023 A novel compound EPIC-0412 reverses temozolomide resistance via inhibiting DNA repair/MGMT in glioblastoma. Neuro-oncology 51 36272139
2017 Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to temozolomide in human glioblastoma. Cancer cell international 50 29225516
2015 Treatment considerations for MGMT-unmethylated glioblastoma. Current neurology and neuroscience reports 49 25394859
2008 Role of mismatch repair and MGMT in response to anticancer therapies. Anti-cancer agents in medicinal chemistry 49 18473722
2018 Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma. Oncogene 47 30542120
2023 Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/β-Catenin and Akt/NF-κB signaling pathways. Phytomedicine : international journal of phytotherapy and phytopharmacology 44 37451151
2024 MGMT in TMZ-based glioma therapy: Multifaceted insights and clinical trial perspectives. Biochimica et biophysica acta. Molecular cell research 40 38242327
2011 O(6)-methylguanine-DNA methyltransferase (MGMT): impact on cancer risk in response to tobacco smoke. Mutation research 39 21708177
2007 MGMT methylation status: the advent of stratified therapy in glioblastoma? Disease markers 39 17325429
2014 The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide. Molecular cancer therapeutics 38 24568970
2007 Genetic association and functional studies of major polymorphic variants of MGMT. DNA repair 38 17569599
2020 Inhibition of MGMT-mediated autophagy suppression decreases cisplatin chemosensitivity in gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 36 32007918
2015 MGMT Expression Predicts PARP-Mediated Resistance to Temozolomide. Molecular cancer therapeutics 36 25777962
2009 MGMT analysis at DNA, RNA and protein levels in glioblastoma tissue. Histology and histopathology 36 19224454
2020 MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas. Frontiers in oncology 33 32039031
2019 Profound, durable and MGMT-independent sensitivity of glioblastoma cells to cyclin-dependent kinase inhibition. International journal of cancer 33 30549269
2019 HDAC8 affects MGMT levels in glioblastoma cell lines via interaction with the proteasome receptor ADRM1. Genes & cancer 33 31798765
2013 MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults. World journal of gastroenterology 33 23716983
2018 MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas. Neurologia medico-chirurgica 32 29848907
2007 MGMT: a personal perspective. DNA repair 32 17482889
2020 The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme. Cancers 29 32354046
2012 O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas. Neurosurgery 28 21822153
2019 Capecitabine and Temozolomide versus FOLFIRI in RAS-Mutated, MGMT-Methylated Metastatic Colorectal Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 27 31740551
2014 Role of MGMT as biomarker in colorectal cancer. World journal of clinical cases 27 25516857
2010 MGMT gene promoter methylation in pediatric glioblastomas. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 27 20585787
2024 Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma. Journal of neuro-oncology 26 38277015
2023 Downregulation of MGMT expression by targeted editing of DNA methylation enhances temozolomide sensitivity in glioblastoma. Neoplasia (New York, N.Y.) 24 37634280
2017 MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas. Pituitary 24 28900805
2016 Posttranslational Regulation of O(6)-Methylguanine-DNA Methyltransferase (MGMT) and New Opportunities for Treatment of Brain Cancers. Mini reviews in medicinal chemistry 24 26202203
2015 MGMT testing allows for personalised therapy in the temozolomide era. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 26518768
2009 Effects of O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms on cancer: a meta-analysis. Mutagenesis 24 19892775
2019 IKBKE enhances TMZ-chemoresistance through upregulation of MGMT expression in glioblastoma. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 23 31865606
2017 Association Between MGMT Promoter Methylation and Breast Cancer: a Meta-Analysis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 23 28848211
2023 Modulating MGMT expression through interfering with cell signaling pathways. Biochemical pharmacology 22 37524206
2013 Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma. BMC cancer 22 23414134
2017 MGMT hypomethylation is associated with DNA damage in workers exposed to low-dose benzene. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 21 28001451
2012 MGMT hypermethylation and MDR system in glioblastoma cancer stem cells. Cancer genomics & proteomics 21 22798502
2020 MGMT expression affects the gemcitabine resistance of pancreatic cancer cells. Life sciences 20 32721465
2014 Immunohistochemical evaluation of O6 -methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma. Neuropathology : official journal of the Japanese Society of Neuropathology 20 24397721
2012 Progress in high-throughput assays of MGMT and APE1 activities in cell extracts. Mutation research 20 22609488
2022 BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression. Cell death & disease 19 36513631
2020 Blocking MAPK/ERK pathway sensitizes hepatocellular carcinoma cells to temozolomide via downregulating MGMT expression. Annals of translational medicine 19 33209885
2019 MGMT Testing in Glioblastomas: Pitfalls and Opportunities. American journal of clinical oncology 19 30444735
2007 Lung cancer risk and variation in MGMT activity and sequence. DNA repair 19 17569600
2022 LncRNA UCA1/miR-182-5p/MGMT axis modulates glioma cell sensitivity to temozolomide through MGMT-related DNA damage pathways. Human pathology 18 35219686
2022 PARP1-MGMT complex underpins pathway crosstalk in O6-methylguanine repair. Journal of hematology & oncology 18 36242092
2020 Critical appraisal of MGMT in digestive NET treated with alkylating agents. Endocrine-related cancer 18 32698158
2016 O6-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer? Lung cancer (Amsterdam, Netherlands) 18 27492578
2020 Tim-3 Expression and MGMT Methylation Status Association With Survival in Glioblastoma. Frontiers in pharmacology 17 33041828
2019 Predictive markers for MGMT promoter methylation in glioblastomas. Neurosurgical review 17 30673883
2018 O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer. Asian Pacific journal of cancer prevention : APJCP 16 29801405
2014 Aberrant DNA methylation of MGMT and hMLH1 genes in prediction of gastric cancer. Genetics and molecular research : GMR 16 24938706
2013 MGMT expression and pituitary tumours: relationship to tumour biology. Pituitary 16 22797801
1990 The control of O6-methylguanine-DNA methyltransferase (MGMT) activity in mammalian cells: a pre-molecular view. Mutation research 16 2233795
2021 Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms. Oncology research 15 34016221
2024 Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in MGMT-methylated glioblastoma. Science translational medicine 14 39356744
2013 Toward a Molecular Classification of Colorectal Cancer: The Role of MGMT. Frontiers in oncology 14 24151575
2022 Clinical strategies to manage adult glioblastoma patients without MGMT hypermethylation. Journal of Cancer 13 34976195
2022 Organochlorine pesticides may induce leukemia by methylation of CDKN2B and MGMT promoters and histone modifications. Gene 13 36261081
2021 Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines. International journal of molecular sciences 13 34202589
2019 Germline variation in O6-methylguanine-DNA methyltransferase (MGMT) as cause of hereditary colorectal cancer. Cancer letters 13 30677446
2017 MGMT gene variants, temozolomide myelotoxicity and glioma risk. A concise literature survey including an illustrative case. Journal of chemotherapy (Florence, Italy) 13 28436299
2024 Enhancing Temozolomide (TMZ) chemosensitivity using CRISPR-dCas9-mediated downregulation of O6-methylguanine DNA methyltransferase (MGMT). Journal of neuro-oncology 12 38762829
2023 Magnolol and Temozolomide exhibit a synergistic anti-glioma activity through MGMT inhibition. Biochimica et biophysica acta. Molecular basis of disease 12 37286145
2018 MGMT gene promoter methylation and its correlation with clinicopathological parameters in glioblastomas. Neurology India 12 30038102

Missed literature

Know a paper Affinage missed for MGMT? Flag it for the maintainers and the community.

No submissions yet.