Low-grade gliomas as neurodevelopmental disorders: Insights from mouse models of neurofibromatosis-1

Over the past few years, the traditional view of brain tumorigenesis has been revolutionized by advances in genomic medicine, molecular biology, stem cell biology and genetically engineered small-animal modelling. We now appreciate that paediatric brain tumours arise following specific genetic mutations in specialized groups of progenitor cells in concert with permissive changes in the local tumour microenvironment. This interplay between preneoplastic/neoplastic cells and non-neoplastic stromal cells is nicely illustrated by the neurofibromatosis type 1-inherited cancer syndrome, in which affected children develop low-grade astrocytic gliomas. In this review, we will use neurofibromatosis type 1 as a model system to highlight the critical role of growth control pathways, non-neoplastic cellular elements and brain region-specific properties in the development of childhood gliomas. The insights derived from examining each of these contributing factors will be instructive in the design of new therapies for gliomas in the paediatric population.