Format

Send to

Choose Destination
Nat Commun. 2018 Feb 23;9(1):810. doi: 10.1038/s41467-018-02826-8.

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

Author information

1
Department of Pathology, University of California, San Francisco, CA, 94143, USA.
2
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.
3
Department of Laboratory Medicine, University of California, San Francisco, CA, 94107, USA.
4
Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, 94115, USA.
5
Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, 11591, Egypt.
6
Departments of Pathology and Neurology, NYU Langone Medical Center, New York, NY, 10016, USA.
7
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
8
Department of Pathology, University of Colorado at Denver, Aurora, CO, 80045, USA.
9
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
10
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
11
Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
12
Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
13
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
14
Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.
15
Department of Pathology, University of California, San Francisco, CA, 94143, USA. david.solomon@ucsf.edu.
16
Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, 94115, USA. david.solomon@ucsf.edu.

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.

PMID:
29476136
PMCID:
PMC5824822
DOI:
10.1038/s41467-018-02826-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center