Pediatric high-grade glioma: a heterogeneous group of neoplasms with different molecular drivers
High-grade gliomas(HGGs) in pediatric age have the same bad prognosis as those arising in adults. Approximately one-half of HGGs in children
occur in the brain stem, most frequently within the pons as diffuse intrinsic pontine glioma or other midline structures. Although they have the
same histological appearance of adult malignant gliomas, in recent years, the extensive use of molecular profiling techniques has demonstrated
significant molecular differences between the two age groups. These data have led to a major reclassification of pediatric HGG (pHGG) based
on molecular subgrouping with significant clinical correlations in terms of age at presentation, anatomical location, and prognosis. The most
important molecular groups are: (1) the histone mutations related pHGG, that is, H3.K27-mutated midline and H3.G34-mutated hemispheric
pHGG; (2) the rare isocitrate dehydrogenase (IDH)-mutated pHGG occurring mainly in adolescents; and (3) the H3-/IDH wild type, a
heterogenous group of pHGG still object of further molecular stratification. Another important group of pHGG is that occurring in patients with
cancer predisposition syndromes such as Li‑Fraumeni syndrome, constitutional mismatch repair deficiency, and neurofibromatosis‑1 (NF1).
In this review, the different subgroups of pHGG and their major driver molecular alterations will be discussed