Fig. 5.

Schematic summary: a The major glioma subtypes arise after specific genetic hits. The tumor phenotypes are then shaped by the tumor microenvironment (TME), its cell composition, epigenetics and additional genetic defects. Different methylation patterns develop in a subtype specific fashion upon tumor progression (left part). On a cellular level, astrocyte-like and oligodendrocyte-like gliomas are both primarily composed of proliferating stem cells, oligodendrocytes and astrocytes, however in different amounts, which associates with different immune cell compositions in the TME and metabolic expression signatures, which partly are affected by methylation effects. b Phenotypic trees provide similarity relations between the expression and methylation subtypes (top), which were simplified as one-dimensional sequences of subtypes and associated with selected transcriptional programs, methylation patterns and prognosis (bottom)