Article
Extent and prognostic relevance of MGMT promotor methylation does not differ between glioblastoma and IDH-wildtype TERT-mutated astrocytoma
Ausmaß und prognostische Relevanz der MGMT Promotor Methylierung unterscheidet sich nicht zwischen Glioblastomen und IDH-Wildtyp TERT mutierten Astrozytomen
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Published: | June 4, 2021 |
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Objective: The cIMPACT-NOW update 6 introduced glioblastoma diagnosis based on the combination of IDH-wildtype status and TERT promotor mutation. MGMT promotor methylation is associated with outcome in glioblastoma as defined by histopathology according to the WHO 2016 classification. However, it is yet unclear whether this is also valid in molecularly defined glioblastoma.
Methods: We searched the institutional database for patients with: 1.) glioblastoma defined by histopathology; and 2.) IDH-wildtype astrocytoma with TERT promotor mutation. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region.
Results: We identified 224 patients with glioblastoma diagnosed based on histopathology, and 71 patients with IDH-wildtype, TERT-mutated astrocytoma including 32 WHO°II and 39 WHO°III astrocytomas. There was no difference in the number of MGMT methylated tumors between the two groups as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two groups (glioblastoma vs IDH-wildtype, TERT-mutated astrocytoma; PFS 9 vs 8 months, p=0.191; OS 18 vs 22 months, p=0.655). In both glioblastoma and IDH-wildtype TERT-mutated astrocytoma higher numbers of methylated CpG sites were associated with prolonged radiographic progression free survival.
Conclusion: Extent of MGMT promotor methylation and its clinical impact is similar in both histopathological glioblastoma and IDH-wildtype, TERT-mutated astrocytoma. Our data appear to support the role of MGMT promotor methylation also in molecularly defined glioblastoma according to the cIMPACT-NOW update 6.