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Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas
The commonest pediatric brain tumors are low-grade gliomas (LGGs). We utilized whole genome sequencing to discover multiple novel genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumo...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2013
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727232/ https://www.ncbi.nlm.nih.gov/pubmed/23583981 http://dx.doi.org/10.1038/ng.2611 |
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| author | Zhang, Jinghui Wu, Gang Miller, Claudia P. Tatevossian, Ruth G. Dalton, James D. Tang, Bo Orisme, Wilda Punchihewa, Chandanamali Parker, Matthew Qaddoumi, Ibrahim Boop, Fredrick A. Lu, Charles Kandoth, Cyriac Ding, Li Lee, Ryan Huether, Robert Chen, Xiang Hedlund, Erin Nagahawatte, Panduka Rusch, Michael Boggs, Kristy Cheng, Jinjun Becksfort, Jared Ma, Jing Song, Guangchun Li, Yongjin Wei, Lei Wang, Jianmin Shurtleff, Sheila Easton, John Zhao, David Fulton, Robert S. Fulton, Lucinda L. Dooling, David J. Vadodaria, Bhavin Mulder, Heather L. Tang, Chunlao Ochoa, Kerri Mullighan, Charles G. Gajjar, Amar Kriwacki, Richard Sheer, Denise Gilbertson, Richard J. Mardis, Elaine R. Wilson, Richard K. Downing, James R. Baker, Suzanne J. Ellison, David W. |
| author_facet | Zhang, Jinghui Wu, Gang Miller, Claudia P. Tatevossian, Ruth G. Dalton, James D. Tang, Bo Orisme, Wilda Punchihewa, Chandanamali Parker, Matthew Qaddoumi, Ibrahim Boop, Fredrick A. Lu, Charles Kandoth, Cyriac Ding, Li Lee, Ryan Huether, Robert Chen, Xiang Hedlund, Erin Nagahawatte, Panduka Rusch, Michael Boggs, Kristy Cheng, Jinjun Becksfort, Jared Ma, Jing Song, Guangchun Li, Yongjin Wei, Lei Wang, Jianmin Shurtleff, Sheila Easton, John Zhao, David Fulton, Robert S. Fulton, Lucinda L. Dooling, David J. Vadodaria, Bhavin Mulder, Heather L. Tang, Chunlao Ochoa, Kerri Mullighan, Charles G. Gajjar, Amar Kriwacki, Richard Sheer, Denise Gilbertson, Richard J. Mardis, Elaine R. Wilson, Richard K. Downing, James R. Baker, Suzanne J. Ellison, David W. |
| author_sort | Zhang, Jinghui |
| collection | PubMed |
| description | The commonest pediatric brain tumors are low-grade gliomas (LGGs). We utilized whole genome sequencing to discover multiple novel genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24/39 (62%) tumors. Intragenic duplications of the FGFR1 tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes containing TKD-duplicated FGFR1 into brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. TKD-duplicated FGFR1 induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs/LGGNTs. |
| format | Online Article Text |
| id | pubmed-3727232 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2013 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-37272322013-12-01 Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Zhang, Jinghui Wu, Gang Miller, Claudia P. Tatevossian, Ruth G. Dalton, James D. Tang, Bo Orisme, Wilda Punchihewa, Chandanamali Parker, Matthew Qaddoumi, Ibrahim Boop, Fredrick A. Lu, Charles Kandoth, Cyriac Ding, Li Lee, Ryan Huether, Robert Chen, Xiang Hedlund, Erin Nagahawatte, Panduka Rusch, Michael Boggs, Kristy Cheng, Jinjun Becksfort, Jared Ma, Jing Song, Guangchun Li, Yongjin Wei, Lei Wang, Jianmin Shurtleff, Sheila Easton, John Zhao, David Fulton, Robert S. Fulton, Lucinda L. Dooling, David J. Vadodaria, Bhavin Mulder, Heather L. Tang, Chunlao Ochoa, Kerri Mullighan, Charles G. Gajjar, Amar Kriwacki, Richard Sheer, Denise Gilbertson, Richard J. Mardis, Elaine R. Wilson, Richard K. Downing, James R. Baker, Suzanne J. Ellison, David W. Nat Genet Article The commonest pediatric brain tumors are low-grade gliomas (LGGs). We utilized whole genome sequencing to discover multiple novel genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24/39 (62%) tumors. Intragenic duplications of the FGFR1 tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes containing TKD-duplicated FGFR1 into brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. TKD-duplicated FGFR1 induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs/LGGNTs. 2013-04-14 2013-06 /pmc/articles/PMC3727232/ /pubmed/23583981 http://dx.doi.org/10.1038/ng.2611 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 Zhang, Jinghui Wu, Gang Miller, Claudia P. Tatevossian, Ruth G. Dalton, James D. Tang, Bo Orisme, Wilda Punchihewa, Chandanamali Parker, Matthew Qaddoumi, Ibrahim Boop, Fredrick A. Lu, Charles Kandoth, Cyriac Ding, Li Lee, Ryan Huether, Robert Chen, Xiang Hedlund, Erin Nagahawatte, Panduka Rusch, Michael Boggs, Kristy Cheng, Jinjun Becksfort, Jared Ma, Jing Song, Guangchun Li, Yongjin Wei, Lei Wang, Jianmin Shurtleff, Sheila Easton, John Zhao, David Fulton, Robert S. Fulton, Lucinda L. Dooling, David J. Vadodaria, Bhavin Mulder, Heather L. Tang, Chunlao Ochoa, Kerri Mullighan, Charles G. Gajjar, Amar Kriwacki, Richard Sheer, Denise Gilbertson, Richard J. Mardis, Elaine R. Wilson, Richard K. Downing, James R. Baker, Suzanne J. Ellison, David W. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title | Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title_full | Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title_fullStr | Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title_full_unstemmed | Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title_short | Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| title_sort | whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727232/ https://www.ncbi.nlm.nih.gov/pubmed/23583981 http://dx.doi.org/10.1038/ng.2611 |
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