SMAD4 and colorectal cancer: The human 5q22.2 and 18q21.1-q21.2 regions are both constantly disrupted in human CRCs [15,16], and encode bona fide CRC driver genes (e.g., APC, SMAD4) as well as genes whose role in cancer etiology remains unclear (e.g., mutated in colorectal cancer or MCC).