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A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas
Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA(D463H) mutation. PRKCA encodes the Protein ki...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2018
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006150/ https://www.ncbi.nlm.nih.gov/pubmed/29915258 http://dx.doi.org/10.1038/s41467-018-04622-w |
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| author | Rosenberg, Shai Simeonova, Iva Bielle, Franck Verreault, Maite Bance, Bertille Le Roux, Isabelle Daniau, Mailys Nadaradjane, Arun Gleize, Vincent Paris, Sophie Marie, Yannick Giry, Marine Polivka, Marc Figarella-Branger, Dominique Aubriot-Lorton, Marie-Hélène Villa, Chiara Vasiljevic, Alexandre Lechapt-Zalcman, Emmanuèle Kalamarides, Michel Sharif, Ariane Mokhtari, Karima Pagnotta, Stefano Maria Iavarone, Antonio Lasorella, Anna Huillard, Emmanuelle Sanson, Marc |
| author_facet | Rosenberg, Shai Simeonova, Iva Bielle, Franck Verreault, Maite Bance, Bertille Le Roux, Isabelle Daniau, Mailys Nadaradjane, Arun Gleize, Vincent Paris, Sophie Marie, Yannick Giry, Marine Polivka, Marc Figarella-Branger, Dominique Aubriot-Lorton, Marie-Hélène Villa, Chiara Vasiljevic, Alexandre Lechapt-Zalcman, Emmanuèle Kalamarides, Michel Sharif, Ariane Mokhtari, Karima Pagnotta, Stefano Maria Iavarone, Antonio Lasorella, Anna Huillard, Emmanuelle Sanson, Marc |
| author_sort | Rosenberg, Shai |
| collection | PubMed |
| description | Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA(D463H) mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot PRKCA(D463H) mutation was not described in other tumors. PRKCA(D463H) is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCα(D463H) mRNA levels are more abundant than wild-type PKCα transcripts, while PKCα(D463H) is less stable than the PCKα(WT) protein. Compared to PCKα(WT), the PKCα(D463H) protein is depleted from the cell membrane. The PKCα(D463H) mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis. |
| format | Online Article Text |
| id | pubmed-6006150 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-60061502018-06-20 A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas Rosenberg, Shai Simeonova, Iva Bielle, Franck Verreault, Maite Bance, Bertille Le Roux, Isabelle Daniau, Mailys Nadaradjane, Arun Gleize, Vincent Paris, Sophie Marie, Yannick Giry, Marine Polivka, Marc Figarella-Branger, Dominique Aubriot-Lorton, Marie-Hélène Villa, Chiara Vasiljevic, Alexandre Lechapt-Zalcman, Emmanuèle Kalamarides, Michel Sharif, Ariane Mokhtari, Karima Pagnotta, Stefano Maria Iavarone, Antonio Lasorella, Anna Huillard, Emmanuelle Sanson, Marc Nat Commun Article Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA(D463H) mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot PRKCA(D463H) mutation was not described in other tumors. PRKCA(D463H) is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCα(D463H) mRNA levels are more abundant than wild-type PKCα transcripts, while PKCα(D463H) is less stable than the PCKα(WT) protein. Compared to PCKα(WT), the PKCα(D463H) protein is depleted from the cell membrane. The PKCα(D463H) mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis. Nature Publishing Group UK 2018-06-18 /pmc/articles/PMC6006150/ /pubmed/29915258 http://dx.doi.org/10.1038/s41467-018-04622-w Text en © The Author(s) 2018 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 Rosenberg, Shai Simeonova, Iva Bielle, Franck Verreault, Maite Bance, Bertille Le Roux, Isabelle Daniau, Mailys Nadaradjane, Arun Gleize, Vincent Paris, Sophie Marie, Yannick Giry, Marine Polivka, Marc Figarella-Branger, Dominique Aubriot-Lorton, Marie-Hélène Villa, Chiara Vasiljevic, Alexandre Lechapt-Zalcman, Emmanuèle Kalamarides, Michel Sharif, Ariane Mokhtari, Karima Pagnotta, Stefano Maria Iavarone, Antonio Lasorella, Anna Huillard, Emmanuelle Sanson, Marc A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title | A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title_full | A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title_fullStr | A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title_full_unstemmed | A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title_short | A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas |
| title_sort | recurrent point mutation in prkca is a hallmark of chordoid gliomas |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006150/ https://www.ncbi.nlm.nih.gov/pubmed/29915258 http://dx.doi.org/10.1038/s41467-018-04622-w |
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