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 two-year survival of less than 20%(1). 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...

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Detalles Bibliográficos
Autores principales: Wu, Gang, Diaz, Alexander K, Paugh, Barbara S, Rankin, Sherri L, Ju, Bensheng, Li, Yongjin, Zhu, Xiaoyan, Qu, Chunxu, Chen, Xiang, Zhang, Junyuan, Easton, John, Edmonson, Michael, Ma, Xiaotu, Lu, Charles, Nagahawatte, Panduka, Hedlund, Erin, Rusch, Michael, Pounds, Stanley, Lin, Tong, Onar-Thomas, Arzu, Huether, Robert, Kriwacki, Richard, Parker, Matthew, Gupta, Pankaj, Becksfort, Jared, Wei, Lei, Mulder, Heather L, Boggs, Kristy, Vadodaria, Bhavin, Yergeau, Donald, Russell, Jake C, Ochoa, Kerri, Fulton, Robert S, Fulton, Lucinda L, Jones, Chris, Boop, Frederick A, Broniscer, Alberto, Wetmore, Cynthia, Gajjar, Amar, Ding, Li, Mardis, Elaine R, Wilson, Richard K, Taylor, Michael R, Downing, James R, Ellison, David W, Zhang, Jinghui, Baker, Suzanne J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056452/
https://www.ncbi.nlm.nih.gov/pubmed/24705251
http://dx.doi.org/10.1038/ng.2938
Descripción
Sumario:Pediatric high-grade glioma (HGG) is a devastating disease with a two-year survival of less than 20%(1). 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 DIPG (32%), in addition to the previously reported frequent somatic mutations in histone H3, TP53 and ATRX in both DIPG and NBS-HGGs(2-5). Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 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%, respectively, of pediatric HGGs, including 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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