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Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma: a retrospective cohort study

  • H. PinsonEmail author
  • G. Hallaert
  • J. Van der Meulen
  • F. Dedeurwaerdere
  • D. Vanhauwaert
  • C. Van den Broecke
  • J. Van Dorpe
  • D. Van Roost
  • J. P. Kalala
  • T. Boterberg
Clinical Study

Abstract

Introduction

Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a “grey zone” of diagnostic uncertainty has been described.

Methods

We performed a retrospective analysis of newly diagnosed glioblastoma patients treated according to the Stupp protocol. Epidemiological data were gathered from the individual patient files. MGMT gene promoter methylation status was determined on stored tumour samples using qMSP. A strong, weak or absent promoter methylation was determined based on Cq values (quantification value) of the MGMT and ACTB primers as well as a positive control sample.

Results

In total, 181 patient files were reviewed and included for statistical analysis. MGMT promoter hypermethylation was detected in 38.7% of glioblastoma patients. The median overall survival of unmethylated and strongly methylated patients was 10.1 months and 19.7 months respectively. Furthermore, 11% of the total patient cohort had a weak MGMT gene promoter methylation. The median OS in this subgroup was 15.4 months, significantly better compared to the unmethylated cohort (P < 0.001). Multivariate Cox regression analysis showed weak MGMT promoter methylation as an independent prognostic parameter for overall survival.

Conclusion

Glioblastoma patients with weak promoter methylation show a statistically significant longer overall survival when compared to clearly unmethylated patients. Patients with grey zone qMSP test results should receive additional molecular analysis in future to further direct individual therapy strategies.

Keywords

Glioblastoma MGMT gene methylation qMSP Prognosis 

Notes

Funding

This work was supported by grants from Ghent University Hospital, Centre for Oncology, from the “Stichting Luka Hemelaere” and “Fonds Arne Lannoy AKA Zorro.”

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to be reported.

Supplementary material

11060_2019_3334_MOESM1_ESM.docx (15 kb)
Supplementary file1 (DOCX 15 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • H. Pinson
    • 1
    Email author
  • G. Hallaert
    • 1
  • J. Van der Meulen
    • 2
  • F. Dedeurwaerdere
    • 3
  • D. Vanhauwaert
    • 4
  • C. Van den Broecke
    • 5
    • 6
  • J. Van Dorpe
    • 5
  • D. Van Roost
    • 1
  • J. P. Kalala
    • 1
  • T. Boterberg
    • 7
  1. 1.Department of NeurosurgeryGhent University HospitalGhentBelgium
  2. 2.Center for Medical GeneticsGhent University HospitalGhentBelgium
  3. 3.Department of PathologyAZ DeltaRoeselareBelgium
  4. 4.Department of NeurosurgeryAZ DeltaRoeselareBelgium
  5. 5.Department of PathologyGhent University HospitalGhentBelgium
  6. 6.Department of PathologyAZ St. Lucas GentGhentBelgium
  7. 7.Department of Radiation OncologyGhent University HospitalGhentBelgium

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