APC and metastatic neoplasm: For example, in patient REACT-001, where no interval chemotherapy was administered, the relative frequency of main driver mutations (APC E1288*, TP53 L125LH, and KRAS G12A) did not change between the primary and metastatic tumors, suggesting that the cluster of cells disseminated from the primary tumor to form the metastatic tumor harbored the entire set of main driver mutations (i.e. the dissemination happens after the occurrence of all above mentioned alterations) (Fig. 2A).