Pediatric gliomas

Abstract

Pediatric gliomas comprise a clinically, histologically, and molecularly very heterogeneous group of CNS tumors. In addition, these tumors are largely different from their counterparts occurring in adults, although they are histologically indistinguishable and uniformly classified by the current WHO classification for CNS tumors. Pilocytic astrocytoma (WHO grade I), mainly arising in the posterior fossa, is the most common representative in children, whereas glioblastoma multiforme (WHO grade IV) predominates in adults. When radical surgical resection is possible in low-grade gliomas, it will likely cure the patient. If complete surgical resection is not possible, however, for example in brainstem gliomas, which are defined by their anatomic localization rather than by their histological or molecular features, therapeutic options are limited and prognosis is usually poor. Recent genome-wide analyses applying different microarray-based methods to investigate DNA copy-number aberrations, mRNA expression signatures, and methylation patterns have shed some light on the pathways involved in the pathogenesis of pediatric glio-mas. Mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling were identified as prominent oncogenic pathways in astrocytic tumors in several studies, whereas NOTCH signaling was implicated in the pathogenesis of a subset of intracranial ependymomas. Future therapeutic strategies targeting these (and other) pathways or conferring epigenetic modifications in the tumor might contribute to a better treatment outcome of patients with unresectable or disseminated tumors at diagnosis. Consideration of reliable molecular markers for outcome prediction will most likely result in a better stratification of patients into different risk groups with adjusted treatment intensity in the future.