MGMT gene variants, temozolomide myelotoxicity and glioma risk. A concise literature survey including an illustrative case

Abstract

Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment. Results indicated the presence of all the rs2308321 (I143 V), rs2308327 (K178R) and rs12917 (L84F) MGMT-variants, which were previously associated with temozolomide myelotoxicity. rs12917 (L84F) variant was reported as associating with lesser risk of gallbladder tumours, yet with higher risk of non-Hodgkin lymphomas related with exposure to chlorinated solvents or hair dyes. DNA repair proteins may exert diverging effects on DNA injuries caused by different chemicals and therefore exerting complex effects on myelotoxicity, antitumour activity and carcinogenesis.

Keywords: Carcinogenesis; Glial tumour; MGMT; Myelotoxicity; Polymorphisms; Variants.