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 ButowskiTarik Tihan, Andrew W. Bollen, Joanna J. Phillips, Arun P. Wiita, Iwei Yeh, Matthew P. Jacobson, Boris C. Bastian, Arie Perry, David A. Solomon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Article number810
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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