Although rare, paediatric high-grade gliomas (pHGG) and Diffuse Midline Gliomas (DMG, including diffuse intrinsic pontine glioma—DIPG) retain both the dramatic prognosis and the canonical deregulated tumour pathways [(RTK)– RAS–PI3K, p53 and RB)] that arise in adults [101]. The gene discussed is RB1; the disease is diffuse intrinsic pontine glioma.