The association between 11C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade II and III gliomas

Clin Radiol. 2020 Aug;75(8):622-628. doi: 10.1016/j.crad.2020.03.033. Epub 2020 Apr 19.

Abstract

Aim: To evaluate the association between 11C-methionine positron-emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas.

Materials and methods: Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine PET as part of their pre-surgical examination. IDH mutation was examined via DNA sequencing, and MGMT promoter methylation via quantitative methylation-specific polymerase chain reaction (PCR).

Results: A threshold of MGMT promoter methylation of 1% was significantly associated with tumour/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1% was higher than that in samples with MGMT promoter methylation <1%, and the difference was statistically significant (p=0.011). Reliable prediction of MGMT promoter methylation (<1% versus ≥1%) was possible using the T/N ratio under the receiver operator characteristic (ROC) curve with a sensitivity and specificity of 75% each (cut-off value=1.6: p=0.0226, area under the ROC curve [AUC]=0.76172). Conversely, the T/N ratio had no association with IDH mutation (p=0.6). The ROC curve revealed no reliable prediction of IDH mutation using the T/N ratio (p=0.606, AUC=0.60577).

Conclusion: 11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • DNA Modification Methylases / genetics*
  • DNA Modification Methylases / metabolism
  • DNA Mutational Analysis
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • DNA, Neoplasm / genetics
  • Female
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Methionine / pharmacokinetics*
  • Middle Aged
  • Mutation*
  • Neoplasm Staging / methods*
  • Positron-Emission Tomography
  • Prognosis
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Tumor Suppressor Proteins
  • Methionine
  • Isocitrate Dehydrogenase
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes