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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

(2020) JOURNAL OF NEURO-ONCOLOGY. 146(1). p.55-62
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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, O-6-METHYLGUANINE-DNA METHYLTRANSFERASE, ADJUVANT TEMOZOLOMIDE, RADIOTHERAPY, HYPERMETHYLATION, CONCOMITANT, PCR

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MLA
Pinson, Harry, et al. “Weak MGMT Gene Promoter Methylation Confers a Clinically Significant Survival Benefit in Patients with Newly Diagnosed Glioblastoma : A Retrospective Cohort Study.” JOURNAL OF NEURO-ONCOLOGY, vol. 146, no. 1, 2020, pp. 55–62, doi:10.1007/s11060-019-03334-5.
APA
Pinson, H., Hallaert, G., Van der Meulen, J., Dedeurwaerdere, F., Vanhauwaert, D., Van den Broecke, C., … Boterberg, T. (2020). Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma : a retrospective cohort study. JOURNAL OF NEURO-ONCOLOGY, 146(1), 55–62. https://doi.org/10.1007/s11060-019-03334-5
Chicago author-date
Pinson, Harry, Giorgio Hallaert, Joni Van der Meulen, F Dedeurwaerdere, D Vanhauwaert, Caroline Van den Broecke, Jo Van Dorpe, Dirk Van Roost, Jean-Pierre Kalala Okito, and Tom Boterberg. 2020. “Weak MGMT Gene Promoter Methylation Confers a Clinically Significant Survival Benefit in Patients with Newly Diagnosed Glioblastoma : A Retrospective Cohort Study.” JOURNAL OF NEURO-ONCOLOGY 146 (1): 55–62. https://doi.org/10.1007/s11060-019-03334-5.
Chicago author-date (all authors)
Pinson, Harry, Giorgio Hallaert, Joni Van der Meulen, F Dedeurwaerdere, D Vanhauwaert, Caroline Van den Broecke, Jo Van Dorpe, Dirk Van Roost, Jean-Pierre Kalala Okito, and Tom Boterberg. 2020. “Weak MGMT Gene Promoter Methylation Confers a Clinically Significant Survival Benefit in Patients with Newly Diagnosed Glioblastoma : A Retrospective Cohort Study.” JOURNAL OF NEURO-ONCOLOGY 146 (1): 55–62. doi:10.1007/s11060-019-03334-5.
Vancouver
1.
Pinson H, Hallaert G, Van der Meulen J, Dedeurwaerdere F, Vanhauwaert D, Van den Broecke C, et al. Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma : a retrospective cohort study. JOURNAL OF NEURO-ONCOLOGY. 2020;146(1):55–62.
IEEE
[1]
H. Pinson et al., “Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma : a retrospective cohort study,” JOURNAL OF NEURO-ONCOLOGY, vol. 146, no. 1, pp. 55–62, 2020.
@article{8639907,
  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.}},
  author       = {{Pinson, Harry and Hallaert, Giorgio and Van der Meulen, Joni and Dedeurwaerdere, F and Vanhauwaert, D and Van den Broecke, Caroline and Van Dorpe, Jo and Van Roost, Dirk and Kalala Okito, Jean-Pierre and Boterberg, Tom}},
  issn         = {{0167-594X}},
  journal      = {{JOURNAL OF NEURO-ONCOLOGY}},
  keywords     = {{Glioblastoma,MGMT gene methylation,qMSP,Prognosis,O-6-METHYLGUANINE-DNA METHYLTRANSFERASE,ADJUVANT TEMOZOLOMIDE,RADIOTHERAPY,HYPERMETHYLATION,CONCOMITANT,PCR}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{55--62}},
  title        = {{Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma : a retrospective cohort study}},
  url          = {{http://dx.doi.org/10.1007/s11060-019-03334-5}},
  volume       = {{146}},
  year         = {{2020}},
}

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