Table 1. . Summary of most frequent molecular and clinical characteristics of pediatric high-grade gliomas.

Mutations/cytogenetics	H3F3AmutK27	H3F3AmutG34	RTK I (PDGFRA ampl.)	SETD2	ACVR1	BRAFV600E	NTRK
Age distribution (years)	5–29	Median: 20	Median: 11.4	>12	5–9	6.5–20	<3
Tumor location	23–43%	12–14%	8–39%	15%	20–22%	10%	40%
Therapeutic Significance	None	None	PDGFR inhibitors	Temozolomide resistance	Potential (ALK inhibitors)	BRAF inhibitors	Potential (NTRK inhibitors)

K27M tumors are found in the midline areas (thalamus, pons, brainstem and spine), they tend to occur at a median age of 10.5 years. G34R/V tumors are found in the cerebral hemispheres, usually occur in adolescents (median age: 18 years) [6,18,20,36,37]. Focal amplifications in PDGFRA are mainly associated with diffuse intrinsic pontine gliomas, the incidence might be overestimated because of the suspected overexpression of PDGFRA in radiation-exposed tumors [6,8,20,68], and with a subset of hemispheric tumors. The median age of patients having tumors with PDGFRA alterations is 11.4 years [6]. Mutations in SETD2 occur exclusively in the cerebral hemispheres in patients older than 12 years [6,40,71]. A recent study found an association between SETD2 mutations and defective DNA mismatch repair through microsatellite instability [41]. Mutations in ACVR1 are reported exclusively in diffuse intrinsic pontine gliomas and are found in 20–22% of these patients, most of which are in pretreated samples [22,58–60]. BRAF ^V600E point mutations in pediatric high-grade gliomas occur in young adults and most of the tumors are located in the cerebral hemispheres [6]. NTRK fusions in NTRK1, NTRK2 and NTRK3 genes are found in the cerebral hemispheres of patients younger than 3 years of age [60].