| Title: |
A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle |
| Authors: |
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 |
| Source: |
Nature Communications, vol 9, iss 1 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2018 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Genetics (rcdc); Cancer (rcdc); Brain Disorders (rcdc); Cancer Genomics (rcdc); Neurosciences (rcdc); Human Genome (rcdc); Brain Cancer (rcdc); Pediatric Research Initiative (rcdc); Rare Diseases (rcdc); Orphan Drug (rcdc); Pediatric Cancer (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Cancer (hrcs-hc); Adult (mesh); Aged (mesh); Cerebral Ventricle Neoplasms (mesh); Extracellular Signal-Regulated MAP Kinases (mesh); Female (mesh); Glioma (mesh); Humans (mesh); Male (mesh); Middle Aged (mesh); Mutation; Missense (mesh); Phosphorylation (mesh); Protein Domains (mesh); Protein Kinase C-alpha (mesh) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt6vd489kc; https://escholarship.org/uc/item/6vd489kc; https://escholarship.org/content/qt6vd489kc/qt6vd489kc.pdf |
| DOI: |
10.1038/s41467-018-02826-8 |
| Availability: |
https://escholarship.org/uc/item/6vd489kc; https://escholarship.org/content/qt6vd489kc/qt6vd489kc.pdf; https://doi.org/10.1038/s41467-018-02826-8 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.65BF06DD |
| Database: |
BASE |