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

Nature communications, 2018-02, Vol.9 (1), p.810-8, Article 810 [Peer Reviewed Journal]

2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2018 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-018-02826-8 ;PMID: 29476136

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Title:
A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle
Author: 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
Subjects: Adult ; Aged ; Astrocytes ; Brain ; Brain cancer ; Brain tumors ; Cerebral Ventricle Neoplasms - enzymology ; Cerebral Ventricle Neoplasms - genetics ; Extracellular signal-regulated kinase ; Extracellular Signal-Regulated MAP Kinases - genetics ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Glial cells ; Glioma ; Glioma - enzymology ; Glioma - genetics ; Humans ; Kinases ; Male ; Middle Aged ; Missense mutation ; Mutation ; Mutation, Missense ; Phosphorylation ; Protein Domains ; Protein kinase C ; Protein Kinase C-alpha - chemistry ; Protein Kinase C-alpha - genetics ; Protein Kinase C-alpha - metabolism ; Third Ventricle - enzymology ; Tumors ; Ventricle ; Ventricles (cerebral)
Is Part Of: Nature communications, 2018-02, Vol.9 (1), p.810-8, Article 810
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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-018-02826-8
PMID: 29476136
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

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

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