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MGMT-Unmethylated Glioblastoma

MedGen UID:
1392081
•Concept ID:
C4330601
•
Neoplastic Process
Synonym: Unmethylated MGMT Glioblastoma

Definition

A glioblastoma characterized by the absence of DNA methylation in the promoter region of the MGMT gene. It is associated with a poor outcome. [from NCI]

Term Hierarchy

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

Professional guidelines

PubMed

Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.
Jue TR, Nozue K, Lester AJ, Joshi S, Schroder LB, Whittaker SP, Nixdorf S, Rapkins RW, Khasraw M, McDonald KL
J Transl Med 2017 Mar 17;15(1):61. doi: 10.1186/s12967-017-1164-1. PMID: 28314386Free PMC Article
Treatment considerations for MGMT-unmethylated glioblastoma.
Taylor JW, Schiff D
Curr Neurol Neurosci Rep 2015 Jan;15(1):507. doi: 10.1007/s11910-014-0507-z. PMID: 25394859

Recent clinical studies

Etiology

Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma.
Rammohan N, Ho A, Saxena M, Bajaj A, Kruser TJ, Horbinski C, Korutz A, Tate M, Sachdev S
J Neurooncol 2022 Jul;158(3):331-339. Epub 2022 May 7 doi: 10.1007/s11060-022-04018-3. PMID: 35525907
Initial Results of a Phase 2 Trial of (18)F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma.
Laack NN, Pafundi D, Anderson SK, Kaufmann T, Lowe V, Hunt C, Vogen D, Yan E, Sarkaria J, Brown P, Kizilbash S, Uhm J, Ruff M, Zakhary M, Zhang Y, Seaberg M, Wan Chan Tseung HS, Kabat B, Kemp B, Brinkmann D
Int J Radiat Oncol Biol Phys 2021 Aug 1;110(5):1383-1395. Epub 2021 Mar 23 doi: 10.1016/j.ijrobp.2021.03.032. PMID: 33771703
Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival.
Hallaert G, Pinson H, Van den Broecke C, Vanhauwaert D, Van Roost D, Boterberg T, Kalala JP
Acta Oncol 2020 Dec;59(12):1474-1479. Epub 2020 Jul 16 doi: 10.1080/0284186X.2020.1794032. PMID: 32672481
Role of postoperative tumor volume in patients with MGMT-unmethylated glioblastoma.
Sales AHA, Bette S, Barz M, Huber T, Wiestler B, Ryang YM, Schmidt-Graf F, Liesche F, Combs SE, Meyer B, Gempt J
J Neurooncol 2019 May;142(3):529-536. Epub 2019 Feb 21 doi: 10.1007/s11060-019-03124-z. PMID: 30790133
MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.
Weller M, Tabatabai G, Kästner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bähr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Hüsing J, Reifenberger G, Wick W; DIRECTOR Study Group
Clin Cancer Res 2015 May 1;21(9):2057-64. Epub 2015 Feb 5 doi: 10.1158/1078-0432.CCR-14-2737. PMID: 25655102

Diagnosis

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
Preconditioning with INC280 and LDK378 drugs sensitizes MGMT-unmethylated glioblastoma to temozolomide: Pre-clinical assessment.
Das A, Alshareef M, Porto GBF, Infinger LK, Vandergrift WA 3rd, Lindhorst SM, Varma AK, Patel SJ, Cachia D
J Neurol Sci 2020 Nov 15;418:117102. Epub 2020 Aug 21 doi: 10.1016/j.jns.2020.117102. PMID: 32866816
Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival.
Hallaert G, Pinson H, Van den Broecke C, Vanhauwaert D, Van Roost D, Boterberg T, Kalala JP
Acta Oncol 2020 Dec;59(12):1474-1479. Epub 2020 Jul 16 doi: 10.1080/0284186X.2020.1794032. PMID: 32672481
Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients.
Chen YY, Ho HL, Lin SC, Ho TD, Hsu CY
Am J Clin Pathol 2018 Mar 29;149(5):412-417. doi: 10.1093/ajcp/aqy008. PMID: 29538610
Treatment considerations for MGMT-unmethylated glioblastoma.
Taylor JW, Schiff D
Curr Neurol Neurosci Rep 2015 Jan;15(1):507. doi: 10.1007/s11910-014-0507-z. PMID: 25394859

Therapy

Preconditioning with INC280 and LDK378 drugs sensitizes MGMT-unmethylated glioblastoma to temozolomide: Pre-clinical assessment.
Das A, Alshareef M, Porto GBF, Infinger LK, Vandergrift WA 3rd, Lindhorst SM, Varma AK, Patel SJ, Cachia D
J Neurol Sci 2020 Nov 15;418:117102. Epub 2020 Aug 21 doi: 10.1016/j.jns.2020.117102. PMID: 32866816
Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival.
Hallaert G, Pinson H, Van den Broecke C, Vanhauwaert D, Van Roost D, Boterberg T, Kalala JP
Acta Oncol 2020 Dec;59(12):1474-1479. Epub 2020 Jul 16 doi: 10.1080/0284186X.2020.1794032. PMID: 32672481
Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients.
Chen YY, Ho HL, Lin SC, Ho TD, Hsu CY
Am J Clin Pathol 2018 Mar 29;149(5):412-417. doi: 10.1093/ajcp/aqy008. PMID: 29538610
Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.
Jue TR, Nozue K, Lester AJ, Joshi S, Schroder LB, Whittaker SP, Nixdorf S, Rapkins RW, Khasraw M, McDonald KL
J Transl Med 2017 Mar 17;15(1):61. doi: 10.1186/s12967-017-1164-1. PMID: 28314386Free PMC Article
Treatment considerations for MGMT-unmethylated glioblastoma.
Taylor JW, Schiff D
Curr Neurol Neurosci Rep 2015 Jan;15(1):507. doi: 10.1007/s11910-014-0507-z. PMID: 25394859

Prognosis

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
Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma.
Rammohan N, Ho A, Saxena M, Bajaj A, Kruser TJ, Horbinski C, Korutz A, Tate M, Sachdev S
J Neurooncol 2022 Jul;158(3):331-339. Epub 2022 May 7 doi: 10.1007/s11060-022-04018-3. PMID: 35525907
Role of postoperative tumor volume in patients with MGMT-unmethylated glioblastoma.
Sales AHA, Bette S, Barz M, Huber T, Wiestler B, Ryang YM, Schmidt-Graf F, Liesche F, Combs SE, Meyer B, Gempt J
J Neurooncol 2019 May;142(3):529-536. Epub 2019 Feb 21 doi: 10.1007/s11060-019-03124-z. PMID: 30790133
Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients.
Chen YY, Ho HL, Lin SC, Ho TD, Hsu CY
Am J Clin Pathol 2018 Mar 29;149(5):412-417. doi: 10.1093/ajcp/aqy008. PMID: 29538610
Treatment considerations for MGMT-unmethylated glioblastoma.
Taylor JW, Schiff D
Curr Neurol Neurosci Rep 2015 Jan;15(1):507. doi: 10.1007/s11910-014-0507-z. PMID: 25394859

Clinical prediction guides

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
Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma.
Rammohan N, Ho A, Saxena M, Bajaj A, Kruser TJ, Horbinski C, Korutz A, Tate M, Sachdev S
J Neurooncol 2022 Jul;158(3):331-339. Epub 2022 May 7 doi: 10.1007/s11060-022-04018-3. PMID: 35525907
Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival.
Hallaert G, Pinson H, Van den Broecke C, Vanhauwaert D, Van Roost D, Boterberg T, Kalala JP
Acta Oncol 2020 Dec;59(12):1474-1479. Epub 2020 Jul 16 doi: 10.1080/0284186X.2020.1794032. PMID: 32672481
Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients.
Chen YY, Ho HL, Lin SC, Ho TD, Hsu CY
Am J Clin Pathol 2018 Mar 29;149(5):412-417. doi: 10.1093/ajcp/aqy008. PMID: 29538610
Treatment considerations for MGMT-unmethylated glioblastoma.
Taylor JW, Schiff D
Curr Neurol Neurosci Rep 2015 Jan;15(1):507. doi: 10.1007/s11910-014-0507-z. PMID: 25394859

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