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- W3113276487 abstract "Abstract Central nervous system high-grade neuroepithelial tumor with BCL6-corepressor alteration (CNS HGNET-BCOR) is a recently identified entity characterized by internal tandem duplication (ITD) of BCOR, a core component of polycomb repressive complex (PRC) 1.1. BCOR-ITD exclusively occurs within an essential binding domain, suggesting aberrant epigenetic activities as a possible mechanism of gliomagenesis; however, the effect of this alteration on the transcriptome and DNA methylation are poorly understood. We have generated new CNS HGNET-BCOR models by lentiviral transduction of the BCOR-ITD into human and murine neural stem cells. In the human model, qRT-PCR and subsequent RNA-seq identified a transient derepression of PRC2-target genes comparing to an isogenic model with overexpression of wildtype-BCOR. A similar effect was found in clinical specimens from previous studies. In the murine-cell model, we confirmed increased clonogenicity in soft-agar assays, and tumors developed in mice flanks. Global DNA methylation levels evaluated by ELISA were significantly lower than those of parent cells, and 177 genes were differentially expressed on RNA-seq analysis comparing to BCOR-overexpressing control cells, including upregulation of known oncogenes. These results suggest that BCOR-ITD and associated alterations in the function of PRC1.1 affect methylation patterns in neural stem cells, driving transcriptional changes and oncogenic transformation into CNS HGNET-BCOR. More detailed analyses, including methylation arrays comparisons with clinical samples and in-silico drug sensitivity testing, are being performed." @default.
- W3113276487 created "2020-12-21" @default.
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- W3113276487 date "2020-12-01" @default.
- W3113276487 modified "2023-09-27" @default.
- W3113276487 title "MODL-04. MODELING CNS HGNET-BCOR PATHOGENESIS USING NEURAL STEM CELLS" @default.
- W3113276487 doi "https://doi.org/10.1093/neuonc/noaa222.581" @default.
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