APC and colorectal cancer: Intriguingly, we found a surprising result that the GPC size under the second rule increased at a relatively early stage, whereas the onset of the GPC could be delayed in the first and last rules, and the mutation sequence frequently found in colorectal cancer, e.g., APC → KRAS → SMAD4 → TP53 in this patient, induced a dramatic increase in the GPC size (Fig. 5h).