Which Cancers are Caused by Activated Proto-Onc Genes?

Proto-onc genes are conserved cellular genes defined by their sequence homology with the transforming (onc) genes of retroviruses. Proto-onc genes differ significantly from viral onc genes both structurally and functionally (1). About twenty different proto-onc genes corresponding to 20 different retroviral onc genes are known (1). At this time the normal function of proto-onc genes has not yet been determined. One of them is structurally related to a growth factor, another to a growth factor receptor (2) and a third one is related to a yeast cell cycle gene (3). It is now widely believed that proto-onc genes can upon transcriptional or mutational activation function like viral onc genes. Activation in oncogene research refers to the conversion of a non-oncogenic proto-onc gene into a carcinogenic variant. Indeed mutationally or transcriptionally altered proto-onc genes have been found in certain tumors. However, the known mutationally or transcriptionally altered proto-onc genes are structurally different from viral onc genes and have not been shown to be the causes of tumors. There is as yet no adequate functional assay for oncogenicity and no consistent correlation between any proto-onc alteration and a certain tumor. As yet viral onc genes are the only proven examples of “activated” proto-onc genes. The proto-onc genes are only a subset of a larger group of cellular genes thought to play a role in cancer (4).