1.Histone K27-mutation: **H3.3 (***H3F3A***) and H3.1 (***HIST1H3B* **and, rarely,**  *HIST1H3C***) mutation at K27**. These cases occur predominantly in mid


**Table 3.**

*WHO grades of pediatric astrocytic tumours [28].*

childhood (median age, approximately 10 years). They are almost exclusively midline, usually present in the thalamus, brain stem, and spinal cord, and carry a very poor prognosis.

H3.3K27M cases are usually present between ages 5 and 10 years, accounting for approximately 60% of cases in the midline and pons. The prognosis for H3.3K27M patients is extremely poor, with a median survival of <1 year [35].

H3.1K27M cases present at a younger age than H3.3K27M cases and are approximately 5 times less frequent. These cases have a slightly more favorable prognosis than do H3.3K27M cases (median survival, 15 vs. 11 months).

2.**H3.3 (***H3F3A***) mutation at G34**: The H3.3G34 subtype is associated with mutations in *TP53* and *ATRX* which show widespread hypomethylation across the whole genome. It is common in older children and young adults (median age, 14–18 years) and arises exclusively in the cerebral cortex [36].

About 5% pediatric high-grade gliomas have *IDH1*-mutation. They are almost exclusively common in older adolescents (median age in a pediatric population, 16 years).

**Pleomorphic xanthoastrocytoma (PXA)-like**: Approximately 10% of pediatric high-grade gliomas have DNA methylation patterns that are PXA-like [37].
