Diffuse intrinsic pontine glioma (
DIPG) is a high-grade
glioma that originates in the pons and is seen exclusively in children. Despite numerous efforts to improve treatment,
DIPG remains incurable with 90% of children dying within 2 y of diagnosis, making it one of the leading causes of death in children with
brain tumors. With the advent of new genomic tools, the genetic landscape of
DIPG is slowly being unraveled. The most common genetic alterations include a K27M mutation in H3.3 or H3.1, which are found in up to 78% of DIPGs, whereas p53 mutations are found in up to 77%. Other recently discovered alterations include amplification of components of the
receptor tyrosine kinase/Ras/
phosphatidylinositol 3-kinase signaling pathway, particularly
platelet-derived growth factor receptor A. Recapitulating such alterations, genetically engineered
DIPG preclinical models have been developed, and
DIPG xenograft models have also been established. Both models have strengths and weaknesses but can help with the prioritization of novel agents for clinical trials for children with
DIPG. As we move forward, it is important that we continue to study the complex and unique biology of
DIPG and develop improved preclinical models to increase our understanding of
DIPG pathogenesis, allowing translation into successful
therapies in the not too distant future.