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

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 Snuderl, Daniel J. Brat, Bette K. Kleinschmidt-DeMasters, Fausto J. Rodriguez, David N. Louis, William H. Yong, M. Beatriz Lopes, Marc K. Rosenblum, Nicholas Butowski, Tarik Tihan, Andrew W. Bollen, Joanna J. Phillips, Arun P. Wiita, Iwei Yeh, Matthew P. Jacobson, Boris C. Bastian, Arie Perry and David A. Solomon ()
Additional contact information
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
Nancy M. Joseph: University of California
Courtney Onodera: University of California
Eric Talevich: University of California
James P. Grenert: 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
Arun P. Wiita: University of California
Iwei Yeh: University of California
Matthew P. Jacobson: University of California
Boris C. Bastian: University of California
Arie Perry: University of California
David A. Solomon: University of California

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-02826-8

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