Strikingly, the sequence of events influencing individual clonal fitness may impact tumor outcome, as a study in a KRASG12D-driven genetically engineered mouse model of colorectal cancer has shown that differently timed sequential combinations of targeted knockout of Apc, Tgfrb2, and Trp53 may greatly impact tumor onset, stage, and the number of metastasis [20]. This evidence concerns the gene APC and neoplasm.