Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782320833993113600 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4056452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wugang thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT diazalexanderk thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT paughbarbaras thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT rankinsherril thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT jubensheng thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT liyongjin thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhuxiaoyan thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT quchunxu thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT chenxiang thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhangjunyuan thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT eastonjohn thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT edmonsonmichael thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT maxiaotu thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT lucharles thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT nagahawattepanduka thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT hedlunderin thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ruschmichael thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT poundsstanley thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT lintong thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT onarthomasarzu thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT huetherrobert thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT kriwackirichard thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT parkermatthew thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT guptapankaj thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT becksfortjared thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT weilei thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT mulderheatherl thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT boggskristy thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT vadodariabhavin thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT yergeaudonald thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT russelljakec thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ochoakerri thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT fultonroberts thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT fultonlucindal thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT joneschris thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT boopfredericka thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT bronisceralberto thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT wetmorecynthia thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT gajjaramar thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT dingli thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT mardiselainer thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT wilsonrichardk thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT taylormichaelr thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT downingjamesr thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ellisondavidw thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhangjinghui thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT bakersuzannej thegenomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT wugang genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT diazalexanderk genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT paughbarbaras genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT rankinsherril genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT jubensheng genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT liyongjin genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhuxiaoyan genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT quchunxu genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT chenxiang genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhangjunyuan genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT eastonjohn genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT edmonsonmichael genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT maxiaotu genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT lucharles genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT nagahawattepanduka genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT hedlunderin genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ruschmichael genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT poundsstanley genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT lintong genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT onarthomasarzu genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT huetherrobert genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT kriwackirichard genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT parkermatthew genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT guptapankaj genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT becksfortjared genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT weilei genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT mulderheatherl genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT boggskristy genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT vadodariabhavin genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT yergeaudonald genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT russelljakec genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ochoakerri genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT fultonroberts genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT fultonlucindal genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT joneschris genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT boopfredericka genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT bronisceralberto genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT wetmorecynthia genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT gajjaramar genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT dingli genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT mardiselainer genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT wilsonrichardk genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT taylormichaelr genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT downingjamesr genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT ellisondavidw genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT zhangjinghui genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma AT bakersuzannej genomiclandscapeofdiffuseintrinsicpontinegliomaandpediatricnonbrainstemhighgradeglioma |