Matano et al. (Matano et al., 2015) used CRISPR - Cas9 gene-editing technology to mutate a series of tumor suppressor genes APC, Smad4, TP53, and oncogenes KRAS, PI3K in normal epithelial organs, and produced corresponding CRC organoids via selective culture in medium without corresponding growth factors. Here, SMAD4 is linked to neoplasm.