APC and colorectal carcinoma: In 1991, multiple research groups first identified APC as a critical gatekeeper gene, demonstrating that its inactivation leads to familial adenomatous polyposis, a syndrome characterized by widespread intestinal polyps and a high risk of CRC.280–282 APC mutations are also common in sporadic tumors, often occurring in the early stages of tumorigenesis.283 The primary mechanism through which the Wnt pathway is activated involves the loss of APC’s negative regulatory function.