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


Authors: Goode, B.; Mondal, G.; Hyun, M.; Ruiz, D. G.; Lin, Y. H.; Van Ziffle, J.; Joseph, N. M.; Onodera, C.; Talevich, E.; Grenert, J. P.; Hewedi, I. H.; Snuderl, M.; Brat, D. J.; Kleinschmidt-DeMasters, B. K.; Rodriguez, F. J.; Louis, D. N.; Yong, W. H.; Lopes, M. B.; Rosenblum, M. K.; Butowski, N.; Tihan, T.; Bollen, A. W.; Phillips, J. J.; Wiita, A. P.; Yeh, I.; Jacobson, M. P.; Bastian, B. C.; Perry, A.; Solomon, D. A.
Article Title: A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle
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. © 2018 The Author(s).
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-02-23
Start Page: 810
Language: English
DOI: 10.1038/s41467-018-02826-8
PROVIDER: scopus
PMCID: PMC5824822
PUBMED: 29476136
DOI/URL:
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    248 Rosenblum