However, the combination of H3K27M with additional mutational events, such as altered cell-cycle regulatory genes (TP53/PPM1D) and growth factor related pathways (ACVR1/PI3KR1), synergistically enhances tumorigenesis and together is thought to be early transformational event in DIPG (26, 32, 33). Here, ACVR1 is linked to diffuse intrinsic pontine glioma.