For example, the CRISPR/Cas9 system was used to introduce mutations in the tumor suppressor genes APC (Adenomatous polyposis coli), SMAD4 (SMAD Family Member 4), and TP53 (Tumor protein P53) and the oncogenes KRAS (KRAS Proto-Oncogene) and PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) in organoids derived from normal or adenoma human intestinal epithelium. Here, SMAD4 is linked to adenoma.