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

• DOI: 10.1038/s41467-018-02826-8
• Publication Date: 2018-02-19T15:10:29Z
• Authors: 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. Kleinsch...; 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; David A. Solomon
• Keywords: Protein kinase domain

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