Skip to main content Skip to main navigation menu Skip to site footer

O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status of high-grade and low-grade gliomas

  • Syaiful Ichwan ,
  • Hesty Lidya Ningsih ,
  • Renindra Ananda Aman ,
  • David Tandian ,
  • Samsul Ashari ,
  • Kevin Gunawan ,
  • Setyo Widi Nugroho ,

Abstract

Background: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA-repair enzyme that correlates with tumor resistance mechanism to chemotherapy. Methylation of the MGMT promoter inhibits the cells from producing MGMT and is useful to predict chemotherapy's effectiveness with alkylating agents. This study aims to evaluate the MGMT promoter methylation of low-grade and high-grade glioma in the Neurosurgery Department of Cipto Mangunkusumo National General Hospital

Methods: We evaluated MGMT promoter methylation status using methylation-specific polymerase chain reaction in low and high-grade glioma patients who underwent surgical resection in the Neurosurgery Department of Cipto Mangunkusomo Hospital Jakarta. The result then correlated with age, sex, Karnofsky Performance Scale (KPS), and glioma grading. Data were analyzed using SPSS version 20 for Windows.

Results: MGMT promoter methylation was observed more often in patients diagnosed with age more than 40 years old than in patients less than 40 years old (85.7% vs. 50.0%), also more in men than women (77.7% vs. 50.0%). In patients with KPS more than 70 and KPS 70 or less, methylation of MGMT promoter was observed in 70.0% and 57.1%, respectively. Based on tumor grading, MGMT promoter methylation was observed more often in low-grade gliomas (WHO grade II) than high-grade gliomas (WHO grade II and IV) (85.7% vs. 50.0%). There was no significant relationship between gender, age, KPS, malignancy degree, and Overall Survival (OS) to the MGMT promoter methylation (p>0.05).

Conclusion:  MGMT promoter methylation was observed less in the higher grade of tumors (grade IV), lower KPS, younger age at the time of diagnosis, and female patients, although the differences were not statistically significant. MGMT promoter methylation was observed more often in gliomas with oligodendroglioma components. 

References

  1. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2(9):494-516.
  2. Chamberlain MC. Treatment options for glioblastoma. Neurosurg Focus. 2006;20(4):E19.
  3. Salvati M, Pichierri A, Piccirilli M, Floriana Brunetto GM, D'Elia A, Artizzu S, et al. Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients. J Neurosurg. 2012 Aug;117(2):204-11.
  4. Barnholtz-Sloan JS, Ostrom QT, Cote D. Epidemiology of Brain Tumors. Neurol Clin. 2018;36(3):395-419.
  5. Wang J, Hu G, Quan X. Analysis of the Factors Affecting the Prognosis of Glioma Patients. Open Med (Wars). 2019;14:331-335.
  6. Silber JR, Bobola MS, Blank A, Chamberlain MC. O(6)-methylguanine-DNA methyltransferase in glioma therapy: promise and problems. Biochim Biophys Acta. 2012;1826(1):71-82.
  7. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000;343(23):1740.
  8. Gunawan PY, Islam AA, July J, Patellongi I, Nasrum M, Aninditha T. Karnofsky Performance Scale and Neurological Assessment of Neuro-Oncology Scale as Early Predictor in Glioma. Asian Pac J Cancer Prev. 2020;21(11):3387-3392.
  9. Brandes AA, Tosoni A, Cavallo G, Reni M, Franceschi E, Bonaldi L, et al. Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: a prospective GICNO study. J Clin Oncol. 2006 Oct 10;24(29):4746-53.
  10. Kamiryo T, Tada K, Shiraishi S, Shinojima N, Kochi M, Ushio Y. Correlation between promoter hypermethylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy. Neurosurgery. 2004;54(2):349-357.
  11. Y?ld?z Çeltek N, Süren M, Demir O, Okan ?. Karnofsky Performance Scale validity and reliability of Turkish palliative cancer patients. Turk J Med Sci. 2019;49(3):894-898.
  12. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190-8.
  13. Weller M, Stupp R, Reifenberger G, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine?. Nat Rev Neurol. 2010;6(1):39-51.
  14. Hsieh CT, Su IC, Huang CJ, Chang CJ, Wang JS. The Prognostic Value of O6-Methylguanine-DNA Methyltransferase Gene Promoter Methylation Detected by Gel-Based Methylation-Specific Polymerase Chain Reaction in Patients with Glioblastoma Multiforme: A Systematic Review. Int J Clin Exp Med. 2016;9(6):10899-10906.
  15. Möllemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G. Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer. 2005;113(3):379-385.
  16. Dong SM, Pang JC, Poon WS, et al. Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors. J Neuropathol Exp Neurol. 2001;60(8):808-816.
  17. Chen Y, Hu F, Zhou Y, Chen W, Shao H, Zhang Y. MGMT promoter methylation and glioblastoma prognosis: a systematic review and meta-analysis. Arch Med Res. 2013;44(4):281-290.
  18. Zhang K, Wang XQ, Zhou B, Zhang L. The prognostic value of MGMT promoter methylation in Glioblastoma multiforme: a meta-analysis. Fam Cancer. 2013;12(3):449-458.

How to Cite

Ichwan, S., Ningsih, H. L., Aman, R. A., Tandian, D., Ashari, S., Gunawan, K., & Nugroho, S. W. (2021). O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status of high-grade and low-grade gliomas. Bali Medical Journal, 10(2), 644–647. https://doi.org/10.15562/bmj.v10i2.2316

HTML
0

Total
16

Share

Search Panel