This suggests a model in which H3.3K27M initiates tumorigenesis in part through epigenetic activation of RAS and MYC and later mutational events act to lock in this activation in a portion of tumours, providing an explanation for the frequent association of PDGFRA/PI3K and MYC alterations in H3.3K27M DIPG (Supplementary Fig. S9). Here, PDGFRA is linked to neoplasm.