ATRX loss ; MGMT ; glioblastoma ; hypermethylation ; low methylation ; methylation status ; temozolomide chemotherapy ; wild-type IDH
Abstract
Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter plays a key role in response to temozolomide chemotherapy and disease prognosis in patients with wild-type isocitrate dehydrogenase (IDH) glioblastoma (GBM).
Patients and methods: The MGMT promoter methylation status and its association with clinicopathological parameters were retrospectively analysed in a cohort of 316 patients with GBM with wild-type IDH.
Results: MGMT methylation was significantly associated with ATRX chromatin remodeler (ATRX) loss and completion of the standard Stupp protocol. The median durations of overall and progression-free survival for the unmethylated, low-methylated (10-39%), and hypermethylated (≥40%) groups were 15, 23, and 30 months and 11, 18, and 21 months, respectively. However, the improvement in the survival of the hypermethylated group was not statistically significant.
Conclusion: We suggest a possible association between MGMT methylation status and ATRX mutations in GBM with wild-type IDH.