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

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 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 mutation was not described in other tumors. PRKCA is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCα mRNA levels are more abundant than wild-type PKCα transcripts, while PKCα is less stable than the PCKα protein. Compared to PCKα, the PKCα protein is depleted from the cell membrane. The PKCα 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006150PMC
http://dx.doi.org/10.1038/s41467-018-04622-wDOI Listing

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