Clinical validation of the CE-IVD marked Therascreen MGMT kit in a cohort of glioblastoma patients

Cancer Biomark. 2017 Dec 6;20(4):435-441. doi: 10.3233/CBM-170191.

Abstract

Background: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76-79.

Methods: We performed a comparison of these two assays to evaluate the potential impact of this shift in analyzed CpGs. Therascreen analysis was centrally performed for 102 glioblastoma patients, who were part of a prospective multicenter trial.

Results: A strong correlation was observed for the mean values of the 4 or 5 analyzed CpGs, with lower values recorded using the Therascreen assay, especially for values greater than 20%. When considering a classification in 3 categories (> 12%: methylated; ⩽ 8%: unmethylated; 9-12%: grey zone), 93% of patients were identically classified between the two assays. Using a binary classification, 95% and 97% of patients were identically classified with cut-offs of 8% and 12%, respectively. A strong prognostic significance was observed for both assays: median overall survival were 15.9 months and 34.9 months for respectively unmethylated and methylated patients with either test.

Conclusion: The results demonstrate that these assays may be used interchangeably.

Keywords: CE-IVD kit; Glioblastoma; MGMT methylation; pyrosequencing.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • CpG Islands
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Genetic Testing
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Reagent Kits, Diagnostic
  • Reproducibility of Results
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Reagent Kits, Diagnostic
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes