A 32-year-old man presents to the ED with a 2-month history of alternating diarrhea and constipation, rectal bleeding, a 20-lb weight loss, and worsening fatigue. What are the most common genetic mutations that could have led to the development of this patient's colon cancer?
A. APC, deleted in colorectal carcinoma (DCC), p53Mutations may cause activation of oncogenes (K-ras) and/or inactivation of tumor suppressor genes (APC, deleted in colo rectal carcinoma [DCC] , p53). Colorectal carcinoma is thought to develop from adenomatous polyps by accumulation of these mutations in what has come to be known as the adenomacarcinoma sequence. The APC gene is a tumor suppressor gene. Mutations in both alleles are necessary to initiate polyp formation. Mutation of K-ras results in an inability to hydrolyze guanosine triphosphate ( GTP), thus leaving the G-protein permanently in the active form. It is thought that this then leads to uncontrolled cell division. MYH is a base excision repair gene, and biallelic deletion results in changes in other downstream molecules. Since its discovery, MYH mutations have been associated with an AFAP phenotype in addition to sporadic cancers. The tumor suppressor gene p53 has been well characterized in a number of malignancies. The p53 protein appears to be crucial for initiating apoptosis in cells with irreparable genetic damage. Mutations in p53 are present in 75% of colorectal cancers.