SMAD4 and colorectal carcinoma: Interestingly, the analysis of genetic data relative to large sets of CRC patients allowed to define the existence of metastasis-associated early driver gene modules present in early tumors and characterized by modules of tumor cells exhibiting CRC drivers (combinations of APC, KRAS, TP53, or SMAD4) associated with potential metastasis-associated genes, such as TCF7L2, AMER1, or PTPRT [56].