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The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.
- Source :
- Nature Genetics; May2014, Vol. 46 Issue 5, p444-450, 7p, 3 Diagrams, 2 Graphs
- Publication Year :
- 2014
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 46
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 95774099
- Full Text :
- https://doi.org/10.1038/ng.2938