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

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
Nature communications | 2018

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.

Pubmed ID: 29915258

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