A. Oncoprint map representing frequency of gene loss (blue bars), mutation (green) and amplification (red) in TCGA analysis of human CRC (www.cbioportal.org). B. Endoscopic images from shRen/Kras/Lgr5 and shApc/Kras/Lgr5 mice, 1 year and 6 weeks post-4OHT, respectively. C. Immunohistochemical (H&E) and immunofluorescent (Ki67, Krt20 and Cleaved-Caspase 3) stains from shRen/Kras, shApc/Kras, shRen/Kras/p53fl/fl and shApc/Kras/p53fl/fl colons following dox treatment for 6 weeks (shApc mice) or 20 weeks (shRen mice). Arrows indicate regions of hyperproliferation driven by KrasG12D, as previously described (). D. Kaplan-Meier plot showing survival of dox-treated shApc (dotted green line, also represented in ), shApc/Kras/Lgr5 (purple line) and shApc/Kras/p53fl/fl/Lgr5 (orange line), following 4OHT treatment at 5-6 weeks of age. E. Blind-scored histological analysis of intestinal sections from shApc/Lgr5, shApc/Kras/Lgr5 and shApc/Kras/p53fl/fl/Lgr5 mice, as indicated. Animals were scored based on most advanced disease evident in an H&E section through the entire intestine. F. H&E stains section of tissue obtained sub-cutaneous transplanted shApc and shApc/Kras organoids/spheroids, 7 weeks following transplant.