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Article

BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

1
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3
Neurosurgical Clinic, Medical Faculty, Heinrich-Heine University Duesseldorf, D-40225 Dusseldorf, Germany
4
Department of Neurosurgery, University of Bonn, D-53127 Bonn, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Christel Herlod-Mende
Int. J. Mol. Sci. 2021, 22(8), 3913; https://doi.org/10.3390/ijms22083913
Received: 1 March 2021 / Revised: 2 April 2021 / Accepted: 6 April 2021 / Published: 10 April 2021
(This article belongs to the Special Issue Molecular Biology and Translational Aspects in CNS Tumors 2.0)
Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors. View Full-Text
Keywords: BCOR; neural stem cells; embryonal tumor; tumor model; polycomb repressive complex; BCORL1 BCOR; neural stem cells; embryonal tumor; tumor model; polycomb repressive complex; BCORL1
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MDPI and ACS Style

Nakata, S.; Yuan, M.; Rubens, J.A.; Kahlert, U.D.; Maciaczyk, J.; Raabe, E.H.; Eberhart, C.G. BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets. Int. J. Mol. Sci. 2021, 22, 3913. https://doi.org/10.3390/ijms22083913

AMA Style

Nakata S, Yuan M, Rubens JA, Kahlert UD, Maciaczyk J, Raabe EH, Eberhart CG. BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets. International Journal of Molecular Sciences. 2021; 22(8):3913. https://doi.org/10.3390/ijms22083913

Chicago/Turabian Style

Nakata, Satoshi, Ming Yuan, Jeffrey A. Rubens, Ulf D. Kahlert, Jarek Maciaczyk, Eric H. Raabe, and Charles G. Eberhart 2021. "BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets" International Journal of Molecular Sciences 22, no. 8: 3913. https://doi.org/10.3390/ijms22083913

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