Like those in the original tumors, CWH22 and CLM22 organoids harbored mutations in pathways important for CRC initiation and progression, including the WNT (APC mutation), RAS-MAPK (KRAS mutation), and TGF-β (SMAD4 mutation) pathways, as well as KMT2C and CDKN1B mutations (Figure 3A). This evidence concerns the gene SMAD4 and colorectal carcinoma.