APC and invasive carcinoma: 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.