Molecular classification of adult gliomas: recent advances and future perspectives

This review summarizes recent advances in the molecular classification of adult gliomas.

According to the 2016 WHO classification, five main molecular subgroups of adult diffuse gliomas can be distinguished based on the 1p/19q codeletion, isocitrate dehydrogenase (IDH), and histone H3.3 mutation status. In the future, this classification may be further refined based on the integration of additional biomarkers, in particular CDKN2A/B homozygous deletion in IDH-mutant astrocytomas, TERT promoter mutations, EGFR amplification, chromosome 7 gain and chromosome 10 loss in IDH-wildtype astrocytomas, and FGFR1 mutations in midline gliomas. Histone H3.3 G34R/V defines a distinct subgroup of hemispheric IDH-wildtype high-grade gliomas occurring in young patients and FGFR gene fusions characterize a subgroup of IDH-wildtype glioblastomas that could benefit from specific treatment approaches. RNA sequencing may identify targetable gene fusions in circumscribed gliomas lacking classical BRAF alterations. In chordoid gliomas, recurrent PRKCA mutations could serve as a new diagnostic marker. Among comprehensive molecular analysis methods, DNA methylation profiling appears as a particularly powerful approach to identify new molecular subgroups of gliomas and to classify difficult cases.

The classification of adult gliomas may be improved by the integration of additional biomarkers and/or by comprehensive molecular analysis, in particular DNA methylation profiling. The most relevant approach, however, remains to be established.