Fig. 2: Poorly differentiated tumors have molecular signatures similar to clinical NEPC.

a H&E from frozen GEM tumors showing examples of adenocarcinoma, poorly differentiated, and NEPC histology. Images are representative of 20 independent mice. Scale bar: 50 μm. b Violin plot of NEPC scores from PRN GEMs with conventional adenocarcinoma and poorly differentiated/NEPC histologies, as well as PCa, CRPC, and NEPC patient samples. Significance was calculated using one-way ANOVA with Tukey’s multiple comparison test. c Heatmap and hierarchical clustering of poor, squamous, adenocarcinoma, and mixed differentiation foci from GEMs based on the PRN POOR vs. PN ADENO Signature. All castrated mice are of PRN genotype. d Top gene sets related to E2F targets, cell cycle, neuronal development, epigenetic reprogramming, epithelial identity, p53 targets, and AR signaling. UP: log2(FC) >1.5; DOWN: log2(FC) <−1.5, Benjamini-Hochberg adjusted two-sided t-test p < 0.05. e GSEA enrichment plots of Hallmark E2F Targets and Hallmark MYC Targets in poorly differentiated (POOR) vs. adenocarcinoma (ADENO).