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A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle

Author

Listed:
  • Benjamin Goode

    (University of California)

  • Gourish Mondal

    (University of California)

  • Michael Hyun

    (University of California)

  • Diego Garrido Ruiz

    (University of California)

  • Yu-Hsiu Lin

    (University of California)

  • Jessica Van Ziffle

    (University of California
    University of California)

  • Nancy M. Joseph

    (University of California
    University of California)

  • Courtney Onodera

    (University of California)

  • Eric Talevich

    (University of California)

  • James P. Grenert

    (University of California
    University of California)

  • Iman H. Hewedi

    (Ain Shams University)

  • Matija Snuderl

    (NYU Langone Medical Center)

  • Daniel J. Brat

    (Northwestern University Feinberg School of Medicine)

  • Bette K. Kleinschmidt-DeMasters

    (University of Colorado at Denver)

  • Fausto J. Rodriguez

    (Johns Hopkins University School of Medicine)

  • David N. Louis

    (Harvard Medical School)

  • William H. Yong

    (University of California)

  • M. Beatriz Lopes

    (University of Virginia School of Medicine)

  • Marc K. Rosenblum

    (Memorial Sloan Kettering Cancer Center)

  • Nicholas Butowski

    (University of California)

  • Tarik Tihan

    (University of California)

  • Andrew W. Bollen

    (University of California)

  • Joanna J. Phillips

    (University of California
    University of California)

  • Arun P. Wiita

    (University of California
    University of California)

  • Iwei Yeh

    (University of California
    University of California)

  • Matthew P. Jacobson

    (University of California)

  • Boris C. Bastian

    (University of California
    University of California)

  • Arie Perry

    (University of California
    University of California)

  • David A. Solomon

    (University of California
    University of California)

Abstract

Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina terminalis along the anterior wall of the third ventricle. Despite being histologically low-grade, chordoid gliomas are often associated with poor outcome, as their stereotypic location in the third ventricle makes resection challenging and efficacious adjuvant therapies have not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutation in PRKCA in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα). Expression of mutant PRKCA in immortalized human astrocytes led to increased phospho-ERK and anchorage-independent growth that could be blocked by MEK inhibition. These studies define PRKCA as a recurrently mutated oncogene in human cancer and identify a potential therapeutic vulnerability in this uncommon brain tumor.

Suggested Citation

  • Benjamin Goode & Gourish Mondal & Michael Hyun & Diego Garrido Ruiz & Yu-Hsiu Lin & Jessica Van Ziffle & Nancy M. Joseph & Courtney Onodera & Eric Talevich & James P. Grenert & Iman H. Hewedi & Matija, 2018. "A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02826-8
    DOI: 10.1038/s41467-018-02826-8
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