The classical genetic model posits the order of major drivers to be APC, TGF beta, KRAS, and TP53. The relative timing of these mutations is derived from mouse models [6, 7] and observed mutational frequencies at different tumor stages [8], e.g., APC mutations are most frequent in early-stage adenomas and TP53 mutations become frequent only in late-stage carcinomas. The gene discussed is APC; the disease is carcinoma.