The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
By Gang Wu, Alexander K. Diaz, Barbara S. Paugh, Sherri L. Rankin, B. Ju, Yongjin Li, Xiaoyan Zhu, Chunxu Qu, Xiang Chen, Junyuan Zhang and 37 more. Nature Genetics, 2014
963 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Neurology
View Paper: https://www.semanticscholar.org/paper/fd0dbb6c9d4a2406b541adc5960e0ef36b7b978a
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Citations in the corpus
- Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma (2017, background): “…(Paugh et al., 2013; Puget et al., 2012) or certain rare histological variants (e.g., BRAF V600E) (Nicolaides et al., 2011; Schiffman et al., 2010), as well as others seemingly unique to DIPG (e.g., ACVR1) (Buczkowicz et al., 2014; Fontebasso et al., 2014; Taylor et al., 2014a; Wu et al., 2014).”
- Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas (2017, background): “These SLG variants include oncogenic germline variants validated by outside groups, such as the TP53 R248Q alteration confirmed as germline by tumornormal analysis of a pediatric glioma case.(10) SLG variants in cancer genes also associated with earlier age of diagnosis in patients with low-grade gl”