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

Suzanne Baker, Jinghui Zhang and colleagues report the identification of recurrent somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 in 32% of diffuse intrinsic pontine gliomas. Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 yea...

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Vydáno v:	Nature genetics Ročník 46; číslo 5; s. 444 - 450
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.05.2014 Nature Publishing Group
Témata:	45 45/23 45/91 631/208/514/1948 64 64/116 64/60 692/699/67/1922 Activin Receptors, Type I - genetics Age Agriculture Animal Genetics and Genomics Animals Bioinformatics Biomedicine Brain Stem Neoplasms - genetics Cancer Cancer Research Child Children & youth Cohort Studies Computational Biology Gene Expression Profiling Gene Function Gene Fusion - genetics Genes Genetic aspects Genetic research Genomes Genomics Glioma - genetics Gliomas Human Genetics Humans Immunoblotting Immunohistochemistry Kinases letter Medical prognosis Microarray Analysis Mutation Pediatrics Receptor, trkA - genetics Receptor, trkB - genetics Receptor, trkC - genetics Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Signal Transduction - genetics Statistics, Nonparametric Survival Tumors Tumors in children Zebrafish
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	Suzanne Baker, Jinghui Zhang and colleagues report the identification of recurrent somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 in 32% of diffuse intrinsic pontine gliomas. Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis 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 DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX , in both DIPGs and NBS-HGGs 2 , 3 , 4 , 5 . 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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.2938