BCOR internal tandem duplication expression in neural stem cells promotes growth, invasion, and expression of PRC2 targets

Satoshi Nakata, Ming Yuan, Jeffrey A. Rubens, Ulf D. Kahlert, Jarek Maciaczyk, Eric H. Raabe, Charles G. Eberhart

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number3913
JournalInternational journal of molecular sciences
Volume22
Issue number8
DOIs
StatePublished - Apr 2 2021

Keywords

  • BCOR
  • BCORL1
  • Embryonal tumor
  • Neural stem cells
  • Polycomb repressive com-plex
  • Tumor model

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'BCOR internal tandem duplication expression in neural stem cells promotes growth, invasion, and expression of PRC2 targets'. Together they form a unique fingerprint.

Cite this