MGMT Status as a Clinical Biomarker in Glioblastoma

Trends Cancer. 2020 May;6(5):380-391. doi: 10.1016/j.trecan.2020.02.010. Epub 2020 Mar 27.

Abstract

Glioblastoma is the most common primary malignant brain tumor. Although current standard therapy extends median survival to ~15 months, most patients do not have a sustained response to treatment. While O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) promoter methylation status is accepted as a prognostic and promising predictive biomarker in glioblastoma, its value in informing treatment decisions for glioblastoma patients remains debatable. Discrepancies between MGMT promoter methylation status and treatment response in some patients may stem from inconsistencies between MGMT methylation and expression levels in glioblastoma. Here, we discuss MGMT as a biomarker and elucidate the discordance between MGMT methylation, expression, and patient outcome, which currently challenges the implementation of this biomarker in clinical practice.

Keywords: MGMT; biomarker; glioblastoma; neuro-oncology; precision medicine.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Clinical Decision-Making / methods
  • DNA Methylation
  • DNA Mismatch Repair
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Humans
  • Predictive Value of Tests
  • Prognosis
  • Progression-Free Survival
  • Promoter Regions, Genetic / genetics
  • Temozolomide / pharmacology*
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide