A genetically engineered mouse model of NUT carcinoma (CUT&RUN)
We created a genetically engineered mouse model (GEMM) of NC that forms a Brd4-NUTM1 fusion gene upon tamoxifen-induction of Sox2-driven Cre. Two GEMM-derived cell lines were developed whose transcriptomic and epigenetic landscapes, characterized by RNAseq and CUT&RUN, show striking overlap with those of primary GEMM tumors. GEMM primary tumor and cell lines form very large H3K27ac-enriched super-enhancers that are unique to hNC, termed megadomains, that are invariably associated with key hNC-defining transcriptional oncogenic targets, Myc and Trp63. Overall design: Compartive epigenomic profiling analysis of cultured 311E and 317E GEMM-derived cell lines in duplicate, one fresh GEMM tumor sample, and two fresh normal gastric mucosa samples from SOX2-/-BRD4-NUTM1+/- control mice. The 311E cultured cells sampled for this study were treated with DMSO control, ABBV-075 (9nM), or taz (1uM). Compartive epigenomic profiling analysis of cultured 311E GEMM-derived cell lines in duplicate. The 311E cultured cells sampled for this study were treated with DMSO control and ABBV-075 (9nM) for 96hrs.