A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas

Shai Rosenberg, Iva Simeonova, Franck Bielle, Maite Verreault, Bertille Bance, Isabelle 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 and Marc Sanson ()
Additional contact information
Shai Rosenberg: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Iva Simeonova: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Franck Bielle: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Maite Verreault: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Bertille Bance: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Isabelle Roux: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Mailys Daniau: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Arun Nadaradjane: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Vincent Gleize: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Sophie Paris: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Yannick Marie: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Marine Giry: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Marc Polivka: AP-HP, Hôpital Lariboisière
Dominique Figarella-Branger: Assistance Publique-Hôpitaux de Marseille (AP-HM), CHU Timone
Marie-Hélène Aubriot-Lorton: CHU Dijon Bourgogne
Chiara Villa: Foch Hospital
Alexandre Vasiljevic: Groupement Hospitalier Est, Hospices Civils de Lyon
Emmanuèle Lechapt-Zalcman: CHU de Caen, Caen, France Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/LDM-TEP Group
Michel Kalamarides: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Ariane Sharif: INSERM U1172, “Development and Plasticity of the Neuroendocrine Brain”
Karima Mokhtari: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Stefano Maria Pagnotta: Università degli Studi del Sannio
Antonio Iavarone: Columbia University Medical Center
Anna Lasorella: Columbia University Medical Center
Emmanuelle Huillard: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
Marc Sanson: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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. PRKCA D463H is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCαD463H mRNA levels are more abundant than wild-type PKCα transcripts, while PKCαD463H is less stable than the PCKαWT protein. Compared to PCKαWT, the PKCαD463H protein is depleted from the cell membrane. The PKCαD463H 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.

Date: 2018
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DOI: 10.1038/s41467-018-04622-w

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