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


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.

DOI: 10.1038/ng.2938

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@inproceedings{Wu2014TheGL, title={The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma}, author={Gang Wu and Alexander K Diaz and Barbara S Paugh and Sherri L Rankin and Bensheng Ju and Yongjin Li and Xiaoyan Zhu and Chunxu Qu and Xiang Chen and Junyuan Zhang and John Easton and Michael Edmonson and Xiaotu Ma and Charles Lu and Panduka Nagahawatte and Erin Hedlund and Michael Rusch and Stanley Pounds and Tong Lin and Arzu Onar-Thomas and Robert Huether and Richard Kriwacki and Matthew Parker and Pankaj Gupta and Jared Becksfort and Lei Wei and Heather L Mulder and Kristy Boggs and Bhavin Vadodaria and Donald Yergeau and Jake C Russell and Kerri Ochoa and Robert S Fulton and Lucinda L Fulton and Chris Jones and Frederick A Boop and Alberto Broniscer and Cynthia Wetmore and Amar Gajjar and Li Ding and Elaine R Mardis and Richard K Wilson and Michael R Taylor and James R Downing and David W Ellison and Jinghui Zhang and Suzanne J Baker}, booktitle={Nature genetics}, year={2014} }