Although many indels and sporadic point mutations were observed genome-wide in late-passage Apc+/−;Bmal1−/− organoids, no consistent mutations were identified in each of the four organoid lines corresponding to driver genes of CRC progression, including Kras, Nras, Braf, p53, Smad4, Pik3ca, and c-Myc (fig. This evidence concerns the gene SMAD4 and colorectal carcinoma.