Abstract: Background and purpose: Temozolomide (TMZ) is the only drug available for the treatment of glioblastoma, and O⁶-methylguanine-DNA methyltransferase (MGMT) promotor methylation is the only gene for prediction of the sensitivity of TMZ in glioblastoma patients. However, detecting the status of MGMT gene methylation alone is not sufficient for evaluating the sensitivity to TMZ. One reason is that the current MGMT detection is qualitative and it is not quantitative. Another reason is that detection of MGMT gene methylation just reflects one of the three DNA repair pathways. The other two repair pathways are not tested. Methods: In this study, we used high resolution melting (HRM) analysis to qualify the methylation status of the patients’ samples, and then measured mRNA levels of N-methylpurine DNA glycosylase (MPG) and human alkane hydroxylase gene homolog 2 (ALKBH2) in the other two pathways by polymerase chain reaction (PCR). Furthermore, the expression levels of MPG and ALKBH2 were divided into high and low expressions, respectively. Results: We found that patients with triple positive test results were more resistant to TMZ whereas patients with triple negative test results were more sensitive to TMZ. The results were consistent with the survival data. Patients with triple negative test results survived the longest, while patients with triple positive test results survived the shortest. Conclusion: Our results suggest that this novel method may predict TMZ sensitivity more precisely in glioblastoma patients.

Key words: Temozolomide, O⁶-methylguanine-DNA methyltransferase, N-methylpurine DNA glycosylase, Alkane hydroxylase gene homolog 2