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Nat Med. 2014 Dec;20(12):1394-6. doi: 10.1038/nm.3716. Epub 2014 Nov 17.

Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.

Author information

1
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
2
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
3
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
4
Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
5
Department of Urology, University of California, San Francisco, San Francisco, California, USA.
6
1] Department of Pathology, University of California, San Francisco, San Francisco, California, USA. [2] Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.
7
1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Neurology, University of California, San Francisco, San Francisco, California, USA. [3] Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
8
Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.

Abstract

Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.

PMID:
25401693
PMCID:
PMC4257862
DOI:
10.1038/nm.3716
[Indexed for MEDLINE]
Free PMC Article

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