Nature communications · 2018
A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Goode Benjamin, Mondal Gourish, Hyun Michael, Ruiz Diego Garrido, Lin Yu-Hsiu, Van Ziffle Jessica, Joseph Nancy M, Onodera Courtney, Talevich Eric, Grenert James P, Hewedi Iman H, Snuderl Matija, Brat Daniel J, Kleinschmidt-DeMasters Bette K, Rodriguez Fausto J, Louis David N, Yong William H, Lopes M Beatriz, Rosenblum Marc K, Butowski Nicholas, Tihan Tarik, Bollen Andrew W, Phillips Joanna J, Wiita Arun P, Yeh Iwei, Jacobson Matthew P, Bastian Boris C, Perry Arie, Solomon David A
Аннотация
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.