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MGMT-Methylated Glioblastoma

MedGen UID:
1656515
•Concept ID:
C4727587
•
Neoplastic Process
Synonym: Methylated MGMT Glioblastoma

Definition

A glioblastoma characterized by the presence of DNA methylation in the promoter region of the MGMT gene. It is associated with improved survival. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMGMT-Methylated Glioblastoma

Professional guidelines

PubMed

Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.
Ganesa S, Sule A, Sundaram RK, Bindra RS
Sci Rep 2022 Apr 6;12(1):5827. doi: 10.1038/s41598-022-09614-x. PMID: 35388070Free PMC Article
Combination chemotherapy versus temozolomide for patients with methylated MGMT (m-MGMT) glioblastoma: results of computational biological modeling to predict the magnitude of treatment benefit.
Castro M, Pampana A, Alam A, Parashar R, Rajagopalan S, Lala DA, Roy KGG, Basu S, Prakash A, Nair P, Joseph V, Agarwal A, G P, Behura L, Kulkarni S, Choudhary NR, Kapoor S
J Neurooncol 2021 Jul;153(3):393-402. Epub 2021 Jun 8 doi: 10.1007/s11060-021-03780-0. PMID: 34101093Free PMC Article
The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients.
McDonald KL, Rapkins RW, Olivier J, Zhao L, Nozue K, Lu D, Tiwari S, Kuroiwa-Trzmielina J, Brewer J, Wheeler HR, Hitchins MP
Eur J Cancer 2013 Jan;49(2):360-8. Epub 2012 Sep 10 doi: 10.1016/j.ejca.2012.08.012. PMID: 22975219

Recent clinical studies

Etiology

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.
Weller J, Schäfer N, Schaub C, Tzaridis T, Zeyen T, Schneider M, Potthoff AL, Giordano FA, Steinbach JP, Zeiner PS, Kowalski T, Sabel M, Hau P, Krex D, Grauer O, Goldbrunner R, Schnell O, Tabatabai G, Ringel F, Schmidt-Graf F, Brehmer S, Tonn JC, Bullinger L, Vajkoczy P, Glas M, Vatter H, Herrlinger U, Seidel C
J Neurooncol 2023 Jan;161(1):147-153. Epub 2023 Jan 7 doi: 10.1007/s11060-022-04203-4. PMID: 36609807Free PMC Article
Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.
Ganesa S, Sule A, Sundaram RK, Bindra RS
Sci Rep 2022 Apr 6;12(1):5827. doi: 10.1038/s41598-022-09614-x. PMID: 35388070Free PMC Article
Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.
Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bähr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schäfer N
Lancet Oncol 2019 Oct;20(10):1444-1453. Epub 2019 Sep 2 doi: 10.1016/S1470-2045(19)30502-9. PMID: 31488360
The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.
Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL
Neuro Oncol 2015 Dec;17(12):1589-98. Epub 2015 Apr 24 doi: 10.1093/neuonc/nov064. PMID: 25910840Free PMC Article
The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients.
McDonald KL, Rapkins RW, Olivier J, Zhao L, Nozue K, Lu D, Tiwari S, Kuroiwa-Trzmielina J, Brewer J, Wheeler HR, Hitchins MP
Eur J Cancer 2013 Jan;49(2):360-8. Epub 2012 Sep 10 doi: 10.1016/j.ejca.2012.08.012. PMID: 22975219

Diagnosis

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.
Weller J, Schäfer N, Schaub C, Tzaridis T, Zeyen T, Schneider M, Potthoff AL, Giordano FA, Steinbach JP, Zeiner PS, Kowalski T, Sabel M, Hau P, Krex D, Grauer O, Goldbrunner R, Schnell O, Tabatabai G, Ringel F, Schmidt-Graf F, Brehmer S, Tonn JC, Bullinger L, Vajkoczy P, Glas M, Vatter H, Herrlinger U, Seidel C
J Neurooncol 2023 Jan;161(1):147-153. Epub 2023 Jan 7 doi: 10.1007/s11060-022-04203-4. PMID: 36609807Free PMC Article
Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS.
Weller J, Schäfer N, Schaub C, Potthoff AL, Steinbach JP, Schlegel U, Sabel M, Hau P, Seidel C, Krex D, Goldbrunner R, Pietsch T, Tzaridis T, Zeyen T, Borger V, Güresir E, Vatter H, Herrlinger U, Schneider M
J Neurooncol 2022 Aug;159(1):95-101. Epub 2022 Jun 15 doi: 10.1007/s11060-022-04046-z. PMID: 35704157Free PMC Article
Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.
Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bähr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schäfer N
Lancet Oncol 2019 Oct;20(10):1444-1453. Epub 2019 Sep 2 doi: 10.1016/S1470-2045(19)30502-9. PMID: 31488360
The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact on patients with MGMT methylated glioblastoma.
Hsu CY, Ho HL, Lin SC, Ho TD, Ho DM
PLoS One 2017;12(10):e0186430. Epub 2017 Oct 16 doi: 10.1371/journal.pone.0186430. PMID: 29036186Free PMC Article
The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients.
McDonald KL, Rapkins RW, Olivier J, Zhao L, Nozue K, Lu D, Tiwari S, Kuroiwa-Trzmielina J, Brewer J, Wheeler HR, Hitchins MP
Eur J Cancer 2013 Jan;49(2):360-8. Epub 2012 Sep 10 doi: 10.1016/j.ejca.2012.08.012. PMID: 22975219

Therapy

Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS.
Weller J, Schäfer N, Schaub C, Potthoff AL, Steinbach JP, Schlegel U, Sabel M, Hau P, Seidel C, Krex D, Goldbrunner R, Pietsch T, Tzaridis T, Zeyen T, Borger V, Güresir E, Vatter H, Herrlinger U, Schneider M
J Neurooncol 2022 Aug;159(1):95-101. Epub 2022 Jun 15 doi: 10.1007/s11060-022-04046-z. PMID: 35704157Free PMC Article
Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.
Ganesa S, Sule A, Sundaram RK, Bindra RS
Sci Rep 2022 Apr 6;12(1):5827. doi: 10.1038/s41598-022-09614-x. PMID: 35388070Free PMC Article
Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy-the MecMeth/NOA-24 trial.
Zeyen T, Potthoff AL, Nemeth R, Heiland DH, Burger MC, Steinbach JP, Hau P, Tabatabai G, Glas M, Schlegel U, Grauer O, Krex D, Schnell O, Goldbrunner R, Sabel M, Thon N, Delev D, Clusmann H, Seidel C, Güresir E, Schmid M, Schuss P, Giordano FA, Radbruch A, Becker A, Weller J, Schaub C, Vatter H, Schilling J, Winkler F, Herrlinger U, Schneider M
Trials 2022 Jan 19;23(1):57. doi: 10.1186/s13063-021-05977-0. PMID: 35045869Free PMC Article
Paradoxical epigenetic regulation of XAF1 mediates plasticity towards adaptive resistance evolution in MGMT-methylated glioblastoma.
Wu Q, Berglund AE, Wang D, MacAulay RJ, Mulé JJ, Etame AB
Sci Rep 2019 Oct 1;9(1):14072. doi: 10.1038/s41598-019-50489-2. PMID: 31575897Free PMC Article
Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.
Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bähr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schäfer N
Lancet Oncol 2019 Oct;20(10):1444-1453. Epub 2019 Sep 2 doi: 10.1016/S1470-2045(19)30502-9. PMID: 31488360

Prognosis

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.
Weller J, Schäfer N, Schaub C, Tzaridis T, Zeyen T, Schneider M, Potthoff AL, Giordano FA, Steinbach JP, Zeiner PS, Kowalski T, Sabel M, Hau P, Krex D, Grauer O, Goldbrunner R, Schnell O, Tabatabai G, Ringel F, Schmidt-Graf F, Brehmer S, Tonn JC, Bullinger L, Vajkoczy P, Glas M, Vatter H, Herrlinger U, Seidel C
J Neurooncol 2023 Jan;161(1):147-153. Epub 2023 Jan 7 doi: 10.1007/s11060-022-04203-4. PMID: 36609807Free PMC Article
Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.
Ganesa S, Sule A, Sundaram RK, Bindra RS
Sci Rep 2022 Apr 6;12(1):5827. doi: 10.1038/s41598-022-09614-x. PMID: 35388070Free PMC Article
Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.
Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bähr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schäfer N
Lancet Oncol 2019 Oct;20(10):1444-1453. Epub 2019 Sep 2 doi: 10.1016/S1470-2045(19)30502-9. PMID: 31488360
The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact on patients with MGMT methylated glioblastoma.
Hsu CY, Ho HL, Lin SC, Ho TD, Ho DM
PLoS One 2017;12(10):e0186430. Epub 2017 Oct 16 doi: 10.1371/journal.pone.0186430. PMID: 29036186Free PMC Article
Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.
Sciuscio D, Diserens AC, van Dommelen K, Martinet D, Jones G, Janzer RC, Pollo C, Hamou MF, Kaina B, Stupp R, Levivier M, Hegi ME
Clin Cancer Res 2011 Jan 15;17(2):255-66. Epub 2010 Nov 19 doi: 10.1158/1078-0432.CCR-10-1931. PMID: 21097691

Clinical prediction guides

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.
Weller J, Schäfer N, Schaub C, Tzaridis T, Zeyen T, Schneider M, Potthoff AL, Giordano FA, Steinbach JP, Zeiner PS, Kowalski T, Sabel M, Hau P, Krex D, Grauer O, Goldbrunner R, Schnell O, Tabatabai G, Ringel F, Schmidt-Graf F, Brehmer S, Tonn JC, Bullinger L, Vajkoczy P, Glas M, Vatter H, Herrlinger U, Seidel C
J Neurooncol 2023 Jan;161(1):147-153. Epub 2023 Jan 7 doi: 10.1007/s11060-022-04203-4. PMID: 36609807Free PMC Article
Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS.
Weller J, Schäfer N, Schaub C, Potthoff AL, Steinbach JP, Schlegel U, Sabel M, Hau P, Seidel C, Krex D, Goldbrunner R, Pietsch T, Tzaridis T, Zeyen T, Borger V, Güresir E, Vatter H, Herrlinger U, Schneider M
J Neurooncol 2022 Aug;159(1):95-101. Epub 2022 Jun 15 doi: 10.1007/s11060-022-04046-z. PMID: 35704157Free PMC Article
Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.
Weller J, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Hau P, Krex D, Grauer O, Goldbrunner R, Bähr O, Uhl M, Seidel C, Tabatabai G, Brehmer S, Bullinger L, Galldiks N, Schaub C, Kebir S, Stummer W, Simon M, Fimmers R, Coch C, Glas M, Herrlinger U, Schäfer N
Lancet Oncol 2019 Oct;20(10):1444-1453. Epub 2019 Sep 2 doi: 10.1016/S1470-2045(19)30502-9. PMID: 31488360
The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.
Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL
Neuro Oncol 2015 Dec;17(12):1589-98. Epub 2015 Apr 24 doi: 10.1093/neuonc/nov064. PMID: 25910840Free PMC Article
Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.
Sciuscio D, Diserens AC, van Dommelen K, Martinet D, Jones G, Janzer RC, Pollo C, Hamou MF, Kaina B, Stupp R, Levivier M, Hegi ME
Clin Cancer Res 2011 Jan 15;17(2):255-66. Epub 2010 Nov 19 doi: 10.1158/1078-0432.CCR-10-1931. PMID: 21097691

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