1. A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas.
- Author
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Rosenberg S, Simeonova I, Bielle F, Verreault M, Bance B, Le Roux I, Daniau M, Nadaradjane A, Gleize V, Paris S, Marie Y, Giry M, Polivka M, Figarella-Branger D, Aubriot-Lorton MH, Villa C, Vasiljevic A, Lechapt-Zalcman E, Kalamarides M, Sharif A, Mokhtari K, Pagnotta SM, Iavarone A, Lasorella A, Huillard E, and Sanson M
- Subjects
- Adult, Aged, Cell Proliferation, Cells, Cultured, Cerebral Ventricle Neoplasms metabolism, Female, Glioma metabolism, Humans, Male, Middle Aged, Point Mutation, Protein Kinase C-alpha metabolism, Cerebral Ventricle Neoplasms genetics, Glioma genetics, Protein Kinase C-alpha genetics
- 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 PRKCAD463H mutation was not described in other tumors. PRKCAD463H 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.- Published
- 2018
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