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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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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:
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
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author 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
author_facet 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
author_sort Wu, Gang
collection PubMed
description 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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spelling pubmed-40564522014-11-01 The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma 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 Nat Genet Article 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. 2014-04-06 2014-05 /pmc/articles/PMC4056452/ /pubmed/24705251 http://dx.doi.org/10.1038/ng.2938 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title_full The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title_fullStr The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title_full_unstemmed The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title_short The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
title_sort genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
topic Article
url 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
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