Children are not just little adults: recent advances in understanding of diffuse intrinsic pontine glioma biology.

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Schroeder, KM; Hoeman, CM; Becher, OJ

Published Date

  • January 2014

Published In

Volume / Issue

  • 75 / 1-2

Start / End Page

  • 205 - 209

PubMed ID

  • 24192697

Pubmed Central ID

  • 24192697

Electronic International Standard Serial Number (EISSN)

  • 1530-0447

Digital Object Identifier (DOI)

  • 10.1038/pr.2013.194

Language

  • eng

Conference Location

  • United States