Artikel
TERT promoter mutational status defines distinct subgroups in diffuse IDH wildtype gliomas
Der TERT Promoter Mutationsstatus definiert Subgruppen diffuser IDH-Wildtyp Gliome
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Veröffentlicht: | 26. Juni 2020 |
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Objective: IDH wildtype (wt) WHO grade II-IV gliomas are widely assumed to be associated with poor outcome, although IDH wt status does not warrant poor prognosis in all glial tumours. Further molecular stratification of IDH wt gliomas according to TERT promoter mutational status, EGFR amplification and chromosome 7/10 status has been proposed, since these alterations predict unfavourable clinical course. On the other hand, distinct subgroups of diffuse IDH wt gliomas lacking these molecular alterations, e.g. TERT promoter wildtype (TERT p-wt) diffuse gliomas, seem to behave less aggressively. Here, we investigated IDH wt gliomas WHO grade II and III with respect to their TERT promoter mutational status.
Methods: In total, 126 IDH wt gliomas WHO grade II and III were included. Two neuropathologists, both blinded for molecular and clinical characteristics, reviewed the tissue samples independently. TERT promoter mutational status (C250T/C228T) was analyzed by Sanger sequencing. IDH1/IDH2 mutational status was assessed through pyrosequencing. Progression-free survival (PFS), time to malignization (TTM) and overall survival (OS) were estimated with the Kaplan Meier method. Prognostic factors were obtained through proportional hazard models.
Results: TERT promoter mutation (p-mut) was seen in 38/68 (52.9%) grade II and 38/58 (65.5%) grade III IDH wt gliomas. In IDH wt WHO grade II gliomas, favourable OS was seen in the subpopulation with IDH wt/TERT p-wt status (median OS TERT wt vs. TERT p-mut: 115.0 vs 33.0 months; p < 0.001). Additionally, time to malignization (TTM) was longer in this subgroup (median TTM 112.0 vs 16.0 months; p < 0.001) and patients were younger at time of diagnosis (median age TERT wt vs. TERT p-mut 40.4 vs 64.4 years; p < 0.001).
Conclusion: In WHO grade II gliomas, the prognostic impact of IDH wt status depends on TERT promoter mutational status. IDH wt TERT p-wt WHO grade II gliomas show a favourable clinical course, are characterized by a younger patient age at time of diagnosis and display a longer TTM when compared to IDH wt TERT p-mut gliomas. Nonetheless, these tumours possess the potential to undergo malignant transformation and thus should not be considered as pilocytic-astrocytoma like gliomas in the context of clinical management.