Targeted next-generation sequencing of adult gliomas for retrospective prognostic evaluation and up-front diagnostics

Aims We aimed to reclassify a population-based cohort of 529 adult glioma patients to evaluate the prognostic impact of the 2016 World Health Organization (WHO) central nervous system tumour classification. Moreover, we evaluated the feasibility of gene panel next-generation sequencing (NGS) in daily diagnostics of 225 prospective glioma patients. Methods The retrospective cohort was reclassified according to WHO 2016 criteria by immunohistochemistry for IDH-R132H, fluorescencein situhybridization for 1p/19q-codeletion and gene panel NGS. All tumours of the prospective cohort were subjected to NGS analysis up-front. Results The entire population-based cohort was successfully reclassified according to WHO 2016 criteria. NGS results were obtained for 98% of the prospective patients. Survival analyses in the population-based cohort confirmed three major prognostic subgroups, that is, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas, IDH-mutant astrocytomas and IDH-wildtype glioblastomas. The distinction between WHO grade II and III was prognostic in patients with IDH-mutant astrocytoma. The survival of patients with IDH-wildtype diffuse astrocytomas carryingTERTpromoter mutation and/orEGFRamplification overlapped with the poor survival of IDH-wildtype glioblastoma patients. Conclusions Gene panel NGS proved feasible in daily diagnostics. In addition, our study confirms the prognostic role of glioma classification according to WHO 2016 in a large population-based cohort. Molecular features of glioblastoma in IDH-wildtype diffuse glioma were linked to poor survival corresponding to IDH-wildtype glioblastoma patients. The distinction between WHO grade II and III retained prognostic significance in patients with IDH-mutant diffuse astrocytic gliomas.

Automated summary

The study successfully reclassified a population-based cohort of adult glioma patients based on WHO 2016 criteria, confirming three major prognostic subgroups. The feasibility of gene panel NGS in daily diagnostics was demonstrated, and it was found that molecular features of IDH-wildtype diffuse glioma were linked to poor survival similar to IDH-wildtype glioblastoma patients. The prognostic significance of distinguishing between WHO grade II and III in IDH-mutant diffuse astrocytic gliomas was also retained.