A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas - Aix-Marseille Université Access content directly
Journal Articles Nature Communications Year : 2018

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

Emmanuèle Lechapt-Zalcman
  • Function : Author

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 (PKC$\alpha$) 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. PKC$\alpha$$^{D463H}$ mRNA levels are more abundant than wild-type PKC$\alpha$ transcripts, whilePKC$\alpha$$^{D463H}$ is less stable than the PCK$\alpha$WT protein. Compared to PCK$\alpha$WT, the PKC$\alpha$$^{D463H}$ protein is depleted from the cell membrane. The PKC$\alpha$$^{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.
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hal-01858239 , version 1 (07-01-2019)

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Shai Rosenberg, Iva Simeonova, Franck Bielle, Maïté Verreault, Bertille Bance, et al.. A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas. Nature Communications, 2018, 9 (1), pp.2371. ⟨10.1038/s41467-018-04622-w⟩. ⟨hal-01858239⟩
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