SMAD4 and colorectal cancer: Given that most early-stage colonic adenomas exhibited genetic alterations in APC7, and most colorectal cancer patients with only a single driver mutation had APC mutations (Supplementary Fig. 17), these relationships between early and late mutation events can be reorganized into the complete mutation sequences available from APC to TP53 (Fig. 5g), confirming the most commonly observed sequences of driver mutations, e.g., APC → KRAS → PIK3CA → TP53 and APC → KRAS → SMAD4 → TP536, 38.