ZFIN ID: ZDB-PUB-140617-7
The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
Wu, G., Diaz, A.K., Paugh, B.S., Rankin, S.L., Ju, B., Li, Y., Zhu, X., Qu, C., Chen, X., Zhang, J., Easton, J., Edmonson, M., Ma, X., Lu, C., Nagahawatte, P., Hedlund, E., Rusch, M., Pounds, S., Lin, T., Onar-Thomas, A., Huether, R., Kriwacki, R., Parker, M., Gupta, P., Becksfort, J., Wei, L., Mulder, H.L., Boggs, K., Vadodaria, B., Yergeau, D., Russell, J.C., Ochoa, K., Fulton, R.S., Fulton, L.L., Jones, C., Boop, F.A., Broniscer, A., Wetmore, C., Gajjar, A., Ding, L., Mardis, E.R., Wilson, R.K., Taylor, M.R., Downing, J.R., Ellison, D.W., Zhang, J., Baker, S.J.
Date: 2014
Source: Nature Genetics   46: 444-50 (Journal)
Registered Authors: Ju, Bensheng, Taylor, Michael R., Zhang, Jinghui
Keywords: none
MeSH Terms:
  • Activin Receptors, Type I/genetics*
  • Animals
  • Brain Stem Neoplasms/genetics*
  • Child
  • Cohort Studies
  • Computational Biology
  • Gene Expression Profiling
  • Gene Fusion/genetics
  • Glioma/genetics*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Microarray Analysis
  • Receptor, trkA/genetics
  • Receptor, trkB/genetics
  • Receptor, trkC/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Signal Transduction/genetics*
  • Statistics, Nonparametric
  • Zebrafish
PubMed: 24705251 Full text @ Nat. Genet.
Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.