Cell Growth, Cancer and Oncogenes
Human Oncogenes
Cancer Genes in the Human Genome
Human Oncogenes
Hybridization of retroviral oncogenes probes to animal DNAs, including humans, demonstrated that copies of many of these genes are present in the genomes of these animals. These are not integrated proviruses, but are complete animal genes which contain their own controlling sequences. The normal cellular counterparts of these oncogenes are called protooncogenes. In their normal genetic state, protooncopenes are important components of cellular signalling and transcription activation.
If a protooncogene under goes a somatic mutation, control of cell growth is lost in the cell in which the mutation occurs and cancer can occur. Those protooncogenes which have been shown to mutate in any individual are called cellular oncogenes and are designated by the prefix "c" (i.e. c-myc, c-abl) to distinguish them from the viral oncogenes. Those protooncogenes that have not been found to mutate are called normal oncogenes and are designated "n" (i.e. n-ras).
Research on retroviral oncogenes was being pursued in parallel with the search by cell biologists for genes which control cell signalling and transcriptional control. At that time, in the early 1980s, it was not widely suspected that these researchers were searching for genes with similar function. The advent of DNA sequencing and the establishment of large DNA sequence databases eventually lead to the merger of the two fields. The diagram below shows how the two fields took different routes to realizing that the cellular gene for the epidermal growth factor receptor (EGFR) and the v-erbB oncogene encoded the same gene product.
A final point to consider is the evolutionary origin of retroviral oncogenes. Did oncogenic retroviruses exist first and were their oncogenes deposited into the genome of a primitive animal. Or did a retrovirus obtain a copy of the gene from a primitive animal. The later appears to be the case because all the protooncogenes have introns that are not found in the viral oncogenes. The suggested mechanism is that RNA copies of the protooncogenes (lacking the introns) were ligated into a retrovirus genome (also RNA) and the oncogene was then perpetuated upon subsequent replication of the retrovirus. This would stabilize the new gene in the virus.
Copyright © 1998. Phillip McClean