I am going to add to @MattDMo 's answer a bit.
Proto-oncogenes Function, Developmental Program, and Regulation
Proto-oncogenes are normally functioning genes that are more often than not in the pathways that lead to mitosis and cellular replication. They have important roles in the development, growth, and maintenance of the organism. Proto-oncogene is an accurate description of the genes, but I unfortunately think that sometimes people think that the genes themselves are bad and that isn't the case.
Growth and development in multicellular organisms are highly regulated processes with many checks and balances. Certain cells need to grow in certain places at certain times, and then they need to go into and remain in interphase. If they don't, or they do things at the incorrect times, the multicellular organism will not develop properly or will develop conditions such as cancer.
It is often these points of regulation that become dysregulated when a proto-oncogene becomes oncogenic. If there are regions of allostery that are affected by a mutation in the coding sequence (exon) and a control molecule that represses the activity of the enzyme through conformation change can no longer bind, then that enzyme can remain active, always turned on.
You can also have a situation where you have transcriptional regulators of proto-oncogenes that can be effected making the gene product oncogenic. If there is a mutation in an enhancer (intronic) of the gene that affects the binding kinetics of enhancers leading to a great increase in transcription, this concentrational difference can lead to uncontrolled grown and tumor formation.
You could also have a situation like MattDMo talked about where you generate frameshifts and premature stop codons, though I would think this is more relevant in tumor suppressor gene mutations, as these types of mutations tend to kill the protein rather quickly, but it is possible that it can cause a problem.
There are however other types of mutations that can effect proto-oncogenes, making them oncogenic. One classic example is RAS. RAS is a G-protein that associates with G-Protein Coupled Receptors at the cell surface and transduce signals into the cell leading to the initiation of the cell cycle. In its inactive form, RAS is bound to GDP. When a signaling molecule binds to the plasma membrane receptor it is associated with the RAS molecule, a Guanosine-Exchange Factor removes the bound GDP, and because of concentration, GTP enters the binding pocket and activates RAS, which activates a phosphorylation cascade, leading to transcription of growth factors.
Normally RAS has GTPase activity and will quickly cleave the gamma phosphate of the GTP in its binding pocket, leading to GDP and inactivating itself. However if the mutation were to knock out this GTPase activity from RAS, then it would have no way to cleave the Gamma phosphate, and therefore it would remain activated and continue the signal transduction, even when it should not.
However, the problem does not need to be with RAS to drive RAS to oncogenesis. If RAS GEF becomes hyperactive and starts to exchange GDP for GTP constitutively, whether or not there is a signal, then RAS will constantly be activated, even if it is still able to cleave the Gamma phosphate and inactivate itself. So there can be Cis-acting drivers of oncogenesis and Trans-acting drivers as well.
I am providing you a link to Scitable's page on Proto-oncogenes to Oncogenes to Cancer. It gives the following summary which is a helpful summary:
- Point mutations, deletions, or insertions that lead to a hyperactive
- Point mutations, deletions, or insertions in the promoter region of a proto-oncogene that lead to increased transcription
- Gene amplification events leading to extra chromosomal copies of a proto-oncogene
- Chromosomal translocation events that relocate a proto-oncogene to a new chromosomal site that leads to higher expression
- Chromosomal translocations that lead to a fusion between a proto-oncogene and a second gene, which produces a fusion protein with oncogenic activity