As reported by Matano et al. and Drost et al., it is possible to introduce a series of single mutations to transform an intestinal human organoid to an invasive carcinoma [67, 68] demonstrating that four mutations (APC, KRAS, SMAD4 and TP53) were mandatory to drive this process and that APC and TP53 loss was sufficient to induce chromosomal instability. The gene discussed is TP53; the disease is invasive carcinoma.