Ras

The 21 kD ras protein has intrinsic GTPase activity, which is regulated by other protein factors, and acts as a focal point for several signal transduction pathways. Point mutations have been identified that result in constitutive ras activity. Mutations in ras genes are suggested to be late events in carcinogenesis, and are linked to disease progression. Data on ras mutation in penile cancer are limited.45,46 A recent study reported somatic missense mutations in three of the 28 penile cancer samples, including one mutation (3%) in KRAS and two mutations in HRAS (7%). HRAS and KRAS mutations were found in larger and more advanced tumors. In addition, in the PIK3CA gene eight mutations (29%) were identified. The mutations in ras and PIK3CA were mutually exclusive, suggesting that dysregulation of either the phosphatidylinositol 3-kinase or ras pathway would be sufficient for the development and progression of penile carcinoma.46

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