Proto-oncogenes generation

So far, our story has focused on mutated single proto-oncogenes—for example src or ras—as key entities in the generation of cancer. A little reflection will convince us that the story cannot be that simple. 

Blake, T. J., M. Shapiro, H. C. d. Morse, and W. Y. Langdon. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif Oncogene. 6 653-657.1991. 

An oncogene formed by either of the first two mechanisms encodes an oncoprotein that differs from the normal protein encoded by the corresponding proto-oncogene. In contrast, the other two mechanisms generate oncogenes whose protein products are identical with the normal proteins their oncogenic effect is due to production at higher-than-normal levels or in cells where they normally are not produced. 

Woolford, J. McAuliffe, A. Rohrschneider, L.R. Activation of the feline c-fms proto-oncogene multiple alterations are required to generate a fully transformed phenotype. Cell, 55, 965-977 (1988)... 

---