P08.05 Combined presence of three MGMT gene-polymorphisms in a glioblastoma patient, who developed severe myelosuppression following temozolomide chemotherapy

AbstractIntroduction:Temozolomide chemotherapy can cause thrombocytopenia or neutropenia in 3 and 4 percent of patients, respectively; however pancytopenia cases were very rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced guanine base mutations in the DNA and it is important both for the tumor response and myelotoxic side effects in glioblastoma patients. DNA repair mechanisms exert diverging effects on DNA injuries caused by different mutagens; and hence, the same variants of the same DNA repair genes may differentially influence cytotoxic or tumorigenic DNA damage. Until recently, only one case-series study exists which showed that rs2308321 and rs2308327 variants of the MGMT-gene is related with general myelotoxicity of temozolomide. Another study have reported rs12917 variant of the MGMT-gene in two patients with temozolomide-induced severe myelosuppression.Materials and Methods:We performed full-sequencing of the MGMT gene (via Applied Biosystems Biosequencing®) in a female glioblastoma patient, who developed pancytopenia and sepsis following temozolomide treatment.Results:We have encountered that this patient carried all the rs2308321, rs2308327 and rs12917 variants of the MGMT-gene associated with temozolomide myelotoxicity. Interestingly, rs12917 variant was previously reported to associate with lesser risks of gallbladder cancer and glial tumors and with higher risk of non-Hodgkin lymphomas following exposure to organic chlorinated solvents or hair-dyes.Conclusions:The sum effect of multiple rare variants and/or coexposure to multiple environmental mutagens may have triggered glioblastoma formation and myelotoxicity in this patient. In future, routine full-sequencing of MGMT gene may help to predict patients with high risk of temozolomide-toxicity.