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

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  • Shai Rosenberg

    (Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
    Sharett Institute for Oncology, Hadassah – Hebrew University Medical Center)

  • Iva Simeonova

    (Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM)

  • Franck Bielle

    (Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
    AP-HP, Hôpital de la Pitié-Salpêtrière)

  • 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
    Institut du Cerveau et de la Moelle épinère—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
    AP-HP, Hôpital de la Pitié-Salpêtrière)

  • Ariane Sharif

    (INSERM U1172, “Development and Plasticity of the Neuroendocrine Brain”)

  • Karima Mokhtari

    (Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM
    AP-HP, Hôpital de la Pitié-Salpêtrière)

  • Stefano Maria Pagnotta

    (Università degli Studi del Sannio
    Columbia University Medical Center)

  • Antonio Iavarone

    (Columbia University Medical Center
    Institute for Cancer Genetics, Irving Comprehensive Research Center)

  • Anna Lasorella

    (Columbia University Medical Center
    Institute for Cancer Genetics, Irving Comprehensive Research 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
    Institut du Cerveau et de la Moelle épinère—ICM
    AP-HP, Hôpital de la Pitié-Salpêtrière
    Site de Recherche Intégrée sur le Cancer (SiRIC) “CURAMUS”)

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.

Suggested Citation

  • Shai Rosenberg & Iva Simeonova & Franck Bielle & Maite Verreault & Bertille Bance & Isabelle Roux & Mailys Daniau & Arun Nadaradjane & Vincent Gleize & Sophie Paris & Yannick Marie & Marine Giry & Mar, 2018. "A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04622-w
    DOI: 10.1038/s41467-018-04622-w
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