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

Chordoid glioma is a rare brain tumorthought to arise from specialized glial cells of the lamina terminalisalong 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 ventriclemakes resection challenging and efficacious adjuvant therapieshave not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutationin 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.