Year: 2018
Type: article
Study design: Observational Study
Abstract: 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. PRKC A 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.
Source: Nature Communications
Authors: Shai Rosenberg, Iva Simeonova, Franck Bielle, Maite Verreault, Bertille Bance, Isabelle Le Roux, Mailys Daniau, Arun Nadaradjane, Vincent Gleize, Sophie Paris, Yannick Marie, Marine Giry, Marc Polivka, Dominique Figarella-Branger, Marie-Hélène Aubriot-Lorton, Chiara Villa, Alexandre Vasiljevic, Emmanuèle Lechapt-Zalcman, Michel Kalamarides, Ariane Sharif, Karima Mokhtari, Stefano Maria Pagnotta, Antonio Iavarone, Anna Lasorella, Emmanuelle Huillard, Marc Sanson
Institutions: Centre National de la Recherche Scientifique, Inserm, Hebrew University of Jerusalem, Hadassah Medical Center, Sorbonne Université, Institut du Cerveau, Université Pierre-et-Marie-Curie, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Hôpital Lariboisière, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, CHU Dijon Bourgogne, Hôpital Foch, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Caen Normandie, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux, Université de Caen Normandie, Lille Neurosciences & Cognition, University of Sannio, Columbia University Irving Medical Center
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2807992785