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The transcriptional landscape of Shh medulloblastoma
Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demo...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979819/ https://www.ncbi.nlm.nih.gov/pubmed/33741928 http://dx.doi.org/10.1038/s41467-021-21883-0 |
| _version_ | 1783667344757751808 |
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| author | Skowron, Patryk Farooq, Hamza Cavalli, Florence M. G. Morrissy, A. Sorana Ly, Michelle Hendrikse, Liam D. Wang, Evan Y. Djambazian, Haig Zhu, Helen Mungall, Karen L. Trinh, Quang M. Zheng, Tina Dai, Shizhong Stucklin, Ana S. Guerreiro Vladoiu, Maria C. Fong, Vernon Holgado, Borja L. Nor, Carolina Wu, Xiaochong Abd-Rabbo, Diala Bérubé, Pierre Wang, Yu Chang Luu, Betty Suarez, Raul A. Rastan, Avesta Gillmor, Aaron H. Lee, John J. Y. Zhang, Xiao Yun Daniels, Craig Dirks, Peter Malkin, David Bouffet, Eric Tabori, Uri Loukides, James Doz, François P. Bourdeaut, Franck Delattre, Olivier O. Masliah-Planchon, Julien Ayrault, Olivier Kim, Seung-Ki Meyronet, David Grajkowska, Wieslawa A. Carlotti, Carlos G. de Torres, Carmen Mora, Jaume Eberhart, Charles G. Van Meir, Erwin G. Kumabe, Toshihiro French, Pim J. Kros, Johan M. Jabado, Nada Lach, Boleslaw Pollack, Ian F. Hamilton, Ronald L. Rao, Amulya A. Nageswara Giannini, Caterina Olson, James M. Bognár, László Klekner, Almos Zitterbart, Karel Phillips, Joanna J. Thompson, Reid C. Cooper, Michael K. Rubin, Joshua B. Liau, Linda M. Garami, Miklós Hauser, Peter Li, Kay Ka Wai Ng, Ho-Keung Poon, Wai Sang Yancey Gillespie, G. Chan, Jennifer A. Jung, Shin McLendon, Roger E. Thompson, Eric M. Zagzag, David Vibhakar, Rajeev Ra, Young Shin Garre, Maria Luisa Schüller, Ulrich Shofuda, Tomoko Faria, Claudia C. López-Aguilar, Enrique Zadeh, Gelareh Hui, Chi-Chung Ramaswamy, Vijay Bailey, Swneke D. Jones, Steven J. Mungall, Andrew J. Moore, Richard A. Calarco, John A. Stein, Lincoln D. Bader, Gary D. Reimand, Jüri Ragoussis, Jiannis Weiss, William A. Marra, Marco A. Suzuki, Hiromichi Taylor, Michael D. |
| author_facet | Skowron, Patryk Farooq, Hamza Cavalli, Florence M. G. Morrissy, A. Sorana Ly, Michelle Hendrikse, Liam D. Wang, Evan Y. Djambazian, Haig Zhu, Helen Mungall, Karen L. Trinh, Quang M. Zheng, Tina Dai, Shizhong Stucklin, Ana S. Guerreiro Vladoiu, Maria C. Fong, Vernon Holgado, Borja L. Nor, Carolina Wu, Xiaochong Abd-Rabbo, Diala Bérubé, Pierre Wang, Yu Chang Luu, Betty Suarez, Raul A. Rastan, Avesta Gillmor, Aaron H. Lee, John J. Y. Zhang, Xiao Yun Daniels, Craig Dirks, Peter Malkin, David Bouffet, Eric Tabori, Uri Loukides, James Doz, François P. Bourdeaut, Franck Delattre, Olivier O. Masliah-Planchon, Julien Ayrault, Olivier Kim, Seung-Ki Meyronet, David Grajkowska, Wieslawa A. Carlotti, Carlos G. de Torres, Carmen Mora, Jaume Eberhart, Charles G. Van Meir, Erwin G. Kumabe, Toshihiro French, Pim J. Kros, Johan M. Jabado, Nada Lach, Boleslaw Pollack, Ian F. Hamilton, Ronald L. Rao, Amulya A. Nageswara Giannini, Caterina Olson, James M. Bognár, László Klekner, Almos Zitterbart, Karel Phillips, Joanna J. Thompson, Reid C. Cooper, Michael K. Rubin, Joshua B. Liau, Linda M. Garami, Miklós Hauser, Peter Li, Kay Ka Wai Ng, Ho-Keung Poon, Wai Sang Yancey Gillespie, G. Chan, Jennifer A. Jung, Shin McLendon, Roger E. Thompson, Eric M. Zagzag, David Vibhakar, Rajeev Ra, Young Shin Garre, Maria Luisa Schüller, Ulrich Shofuda, Tomoko Faria, Claudia C. López-Aguilar, Enrique Zadeh, Gelareh Hui, Chi-Chung Ramaswamy, Vijay Bailey, Swneke D. Jones, Steven J. Mungall, Andrew J. Moore, Richard A. Calarco, John A. Stein, Lincoln D. Bader, Gary D. Reimand, Jüri Ragoussis, Jiannis Weiss, William A. Marra, Marco A. Suzuki, Hiromichi Taylor, Michael D. |
| author_sort | Skowron, Patryk |
| collection | PubMed |
| description | Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention. |
| format | Online Article Text |
| id | pubmed-7979819 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-79798192021-04-16 The transcriptional landscape of Shh medulloblastoma Skowron, Patryk Farooq, Hamza Cavalli, Florence M. G. Morrissy, A. Sorana Ly, Michelle Hendrikse, Liam D. Wang, Evan Y. Djambazian, Haig Zhu, Helen Mungall, Karen L. Trinh, Quang M. Zheng, Tina Dai, Shizhong Stucklin, Ana S. Guerreiro Vladoiu, Maria C. Fong, Vernon Holgado, Borja L. Nor, Carolina Wu, Xiaochong Abd-Rabbo, Diala Bérubé, Pierre Wang, Yu Chang Luu, Betty Suarez, Raul A. Rastan, Avesta Gillmor, Aaron H. Lee, John J. Y. Zhang, Xiao Yun Daniels, Craig Dirks, Peter Malkin, David Bouffet, Eric Tabori, Uri Loukides, James Doz, François P. Bourdeaut, Franck Delattre, Olivier O. Masliah-Planchon, Julien Ayrault, Olivier Kim, Seung-Ki Meyronet, David Grajkowska, Wieslawa A. Carlotti, Carlos G. de Torres, Carmen Mora, Jaume Eberhart, Charles G. Van Meir, Erwin G. Kumabe, Toshihiro French, Pim J. Kros, Johan M. Jabado, Nada Lach, Boleslaw Pollack, Ian F. Hamilton, Ronald L. Rao, Amulya A. Nageswara Giannini, Caterina Olson, James M. Bognár, László Klekner, Almos Zitterbart, Karel Phillips, Joanna J. Thompson, Reid C. Cooper, Michael K. Rubin, Joshua B. Liau, Linda M. Garami, Miklós Hauser, Peter Li, Kay Ka Wai Ng, Ho-Keung Poon, Wai Sang Yancey Gillespie, G. Chan, Jennifer A. Jung, Shin McLendon, Roger E. Thompson, Eric M. Zagzag, David Vibhakar, Rajeev Ra, Young Shin Garre, Maria Luisa Schüller, Ulrich Shofuda, Tomoko Faria, Claudia C. López-Aguilar, Enrique Zadeh, Gelareh Hui, Chi-Chung Ramaswamy, Vijay Bailey, Swneke D. Jones, Steven J. Mungall, Andrew J. Moore, Richard A. Calarco, John A. Stein, Lincoln D. Bader, Gary D. Reimand, Jüri Ragoussis, Jiannis Weiss, William A. Marra, Marco A. Suzuki, Hiromichi Taylor, Michael D. Nat Commun Article Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention. Nature Publishing Group UK 2021-03-19 /pmc/articles/PMC7979819/ /pubmed/33741928 http://dx.doi.org/10.1038/s41467-021-21883-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Skowron, Patryk Farooq, Hamza Cavalli, Florence M. G. Morrissy, A. Sorana Ly, Michelle Hendrikse, Liam D. Wang, Evan Y. Djambazian, Haig Zhu, Helen Mungall, Karen L. Trinh, Quang M. Zheng, Tina Dai, Shizhong Stucklin, Ana S. Guerreiro Vladoiu, Maria C. Fong, Vernon Holgado, Borja L. Nor, Carolina Wu, Xiaochong Abd-Rabbo, Diala Bérubé, Pierre Wang, Yu Chang Luu, Betty Suarez, Raul A. Rastan, Avesta Gillmor, Aaron H. Lee, John J. Y. Zhang, Xiao Yun Daniels, Craig Dirks, Peter Malkin, David Bouffet, Eric Tabori, Uri Loukides, James Doz, François P. Bourdeaut, Franck Delattre, Olivier O. Masliah-Planchon, Julien Ayrault, Olivier Kim, Seung-Ki Meyronet, David Grajkowska, Wieslawa A. Carlotti, Carlos G. de Torres, Carmen Mora, Jaume Eberhart, Charles G. Van Meir, Erwin G. Kumabe, Toshihiro French, Pim J. Kros, Johan M. Jabado, Nada Lach, Boleslaw Pollack, Ian F. Hamilton, Ronald L. Rao, Amulya A. Nageswara Giannini, Caterina Olson, James M. Bognár, László Klekner, Almos Zitterbart, Karel Phillips, Joanna J. Thompson, Reid C. Cooper, Michael K. Rubin, Joshua B. Liau, Linda M. Garami, Miklós Hauser, Peter Li, Kay Ka Wai Ng, Ho-Keung Poon, Wai Sang Yancey Gillespie, G. Chan, Jennifer A. Jung, Shin McLendon, Roger E. Thompson, Eric M. Zagzag, David Vibhakar, Rajeev Ra, Young Shin Garre, Maria Luisa Schüller, Ulrich Shofuda, Tomoko Faria, Claudia C. López-Aguilar, Enrique Zadeh, Gelareh Hui, Chi-Chung Ramaswamy, Vijay Bailey, Swneke D. Jones, Steven J. Mungall, Andrew J. Moore, Richard A. Calarco, John A. Stein, Lincoln D. Bader, Gary D. Reimand, Jüri Ragoussis, Jiannis Weiss, William A. Marra, Marco A. Suzuki, Hiromichi Taylor, Michael D. The transcriptional landscape of Shh medulloblastoma |
| title | The transcriptional landscape of Shh medulloblastoma |
| title_full | The transcriptional landscape of Shh medulloblastoma |
| title_fullStr | The transcriptional landscape of Shh medulloblastoma |
| title_full_unstemmed | The transcriptional landscape of Shh medulloblastoma |
| title_short | The transcriptional landscape of Shh medulloblastoma |
| title_sort | transcriptional landscape of shh medulloblastoma |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979819/ https://www.ncbi.nlm.nih.gov/pubmed/33741928 http://dx.doi.org/10.1038/s41467-021-21883-0 |
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