Fig. 4

Proposed scheme for the prognostic classification of diffuse gliomas. Diffuse gliomas are first stratified based on their IDH-mutation status. Further classification is based on the ATRX and/or TP53 mutation status or determining 1p19q codeletion (these changes are mutually exclusive). Within the ATRX and/or TP53 mutated samples, mutations in PI3 kinase genes PIK3CA and PIK3R1 are associated with poor prognosis. It should be noted that there are genetic changes that associate with each molecular subtype (like EGFR amplification with IDH-wt tumors). They are however, not important for prognostic classification and may occur in several molecular subtypes. For example, PI3K mutations occur in all molecular subtypes but are only significantly prognostic in IDH-mutated, TP53/ATRX mutated diffuse gliomas). Additional prognostic factors include tumor grade and patient age, both of which are correlated to the mutational load of the tumor and are listed below the classification scheme. These additional markers are often correlated to the mutational profile of the tumors: Patients with IDH-wt tumors are often older and most are diagnosed as grade IV. ATRX/TP53 indicates mutation of either/both genes; 1p19q indicates codeletion of these chromosomal arms