Recent whole genome sequencing studies have identified mutations in histone genes H3K27M encoding for H3.1 and H3.3 isoforms, as well as in TP53 and ACVR1. Furthermore, up to 36% of DIPG cases exhibit gene amplifications of receptor tyrosine kinases (RTKs) such as platelet-derived growth factor receptor (PDGFR), where as mutations of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) cascade and loss of phosphatase and tensin homolog play a potential role on the oncogenesis of DIPG [4–6]. Here, TP53 is linked to diffuse intrinsic pontine glioma.