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The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma

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the St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project·2014·Nature Genetics
DOI 10.1038/ng.2938
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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.

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Metadata

Authors
the St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2014-04-06
Volume
46
Issue
5
Pages
444-450
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.2938
OpenAlex
W2053349906
Cited by
1,105
References
10
FWCI
42.01
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. https://app.cochat.ai/papers/10.1038/ng.2938
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the St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. (2014). The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nature Genetics. https://doi.org/10.1038/ng.2938

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