SMAD4 and colorectal carcinoma: In particular, they generated human CRC organoids with a combination of mutations of the four most frequently gene alterations reported in CRC by using CRISPR/Cas9 genome editing, such as KRAS G12D mutation and the knockout of APC, P53, and SMAD4, while WNT, EGFR, P53, and TGF-β were present in the normal status.