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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-06-18

AUTHORS

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

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. More... »

PAGES

2371

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • Gaffin Center for Neuro-oncology, Sharett Institute for Oncology, Hadassah – Hebrew University Medical Center, 91120 Jerusalem, Israel
  • Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM, F-75013 Paris, France
  • Laboratoire R Escourolle, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013 Paris, France
  • Onconeurotek Tumor Bank, Institut du Cerveau et de la Moelle épinère—ICM, F-75013 Paris, France
  • Department of Pathology, AP-HP, Hôpital Lariboisière, F-75010 Paris, France
  • Pathology and Neuropathology Department, Assistance Publique-Hôpitaux de Marseille (AP-HM), CHU Timone, 13005 Marseille, France
  • Department of Pathology and CRB Ferdinand Cabanne, CHU Dijon Bourgogne, 21000 Dijon, France
  • Department of Pathological Cytology and Anatomy, Foch Hospital, Suresnes F-92151 Paris, France
  • Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, 69500 Bron, France
  • Department of Pathology, CHU de Caen, Caen, France Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/LDM-TEP Group, 14000 Caen, France
  • Service de Neurochirurgie, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013 Paris, France
  • INSERM U1172, “Development and Plasticity of the Neuroendocrine Brain”, F-59045 Lille, France
  • Institute for Cancer Genetics, Columbia University Medical Center, New York City, NY 10032 USA
  • Departments of Neurology and Pathology, Institute for Cancer Genetics, Irving Comprehensive Research Center, New York, NY 10032 USA
  • Departments of Pediatrics and Pathology, Institute for Cancer Genetics, Irving Comprehensive Research Center, New York, NY 10032 USA
  • Site de Recherche Intégrée sur le Cancer (SiRIC) “CURAMUS”, F-75013 Paris, France
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-04622-w

    DOI

    http://dx.doi.org/10.1038/s41467-018-04622-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104575292

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29915258


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    468 Onconeurotek Tumor Bank, Institut du Cerveau et de la Moelle épinère—ICM, F-75013 Paris, France
    469 schema:name Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM, F-75013 Paris, France
    470 Onconeurotek Tumor Bank, Institut du Cerveau et de la Moelle épinère—ICM, F-75013 Paris, France
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