SMAD4 and colorectal carcinoma: Key genes harboring somatic mutations and/or copy number variations (CNV) in CRC and CRLM [24,25,26] are located in or near the spots (Figure 1d, part below), which includes canonical core CRC drivers (combinations of APC, KRAS, TP53, or SMAD4), which can combine with one additional candidate metastasis driver (TCF7L2, AMER1, or PTPRT) [27].