The most common oncogene abnormality observed in association with colorectal cancer is which of the following?

b. Amplification of the K-ras oncogene

In colon cancer an important genetic alteration that has been demonstrated is a mutation of the K-ras protooncogene. The ras protooncogenes are a family of normal genes (N-ras, H-ras and K-ras) that are highly conserved in nature and encode for the production of GTP-binding proteins (G proteins) which are important for signal transduction. G proteins are involved in the transduction of proliferative signals induced by growth factors or factors involved in cell differentiation. The product of a mutated ras gene is an abnormal G protein which has lost its ability to become inactivated; and thus, results in continuous growth stimulation and autonomous cell growth or differentiation. Experimentally, transfection of normal fibroblasts by mutated ras genes confer neoplastic properties to those cells. About half of colorectal carcinomas and a similar percentage of adenomas larger than 1 cm in diameter have been found to have the ras gene mutations. By contrast, less than 10% of patients with adenomas smaller than 1 cm have this mutation. It has been postulated that the ras gene mutation may be the initiating event in some colorectal carcinomas or, alternatively, may promote the clonal expansion of a mutated cell population. It appears that the ras gene mutation alone is not responsible for tumorigenesis. Other molecular events appear to be required in addition to ras gene mutations.