PIK3CA and neoplasm: DIPGs with more extensive genome or exome sequencing data (n = 154) allowed us to investigate additional co-segregating mutations, and identified a significant enrichment of PI3-kinase pathway alterations (PIK3CA, PIK3R1 and PTEN) in ACVR1 mutant compared with wild-type tumours (22/40, 55% vs 18/114, 15.8%; p < 0.0001), whilst conversely the TP53 pathway was targeted by mutations in TP53 and PPM1D significantly more commonly in ACVR1 wild-type cases (13/40, 32.5% vs 87/114, 76.3%; p < 0.0001, Fisher’s exact test) (Fig. 1e).