Gliomas represent the most common brain tumors. Nowadays, alkylating agents are often used as a treatment for gliomas (eg. temozolomide). These substances lead to alkylation of guanine in DNA in the position O6 and thereby lead to form bonds between adjacent chains in the DNA doublehelix and subsequently to apoptosis. Cell reparative protein MGMT ("O6-methylguanine - DNA methyltransferase") removes this alkylation from guanine and thus cause resistance to alkylating agents. However, if methylation of CpG islands in the promoter MGMT is present this gene is inactivated. Patients with this methylation are sensitive to the treatment with alkylating agents and survive longer. The frequency of methylation of the MGMT promoter in glioblastomas is between 40 - 45%.
Examination
To detect methylation of the promoter MGMT we use MSP - methylation-specific PCR.
References
- M. Esteller et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. 2000. N Engl J Med 343: 1350–1354.
- M.E. Hegi et al. Correlation of O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation With Clinical Outcomes in Glioblastoma and Clinical Strategies to Modulate MGMT Activity. 2008. Journal of Clinical Oncology 26: 4189-4199.
- M. Uno et al. Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma. 2011. Clinics 66(10): 1747-1755.