How to define a candidate to a proto-oncogene, what kinds of test should be performed.
Yes. In addition mutations and virus also capable of transform a normal cell to a cancerous cell.
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There are genes as APC, p53 and RB that frequently are mutated in carcinogenesis process but at least are needed two events (its mutation and consequent mutations). So, answering in a short way, no, it is impossible. There are some chemicals that can induce carcinogenesis in only one dosis process, such as MNU. But even with that chemicals, it is impossible to confirm only one event.
To test a candidate to oncogen, you should look for its involvement in cell control cycle. For humans and mice, there are online metabolomes that you can check. If it is not there and you have no epidemiological data, although it is not impossible that your candidate gen is an oncogen, it would be quite improbable.
After that, you should prove in cell cultures as some other genes can compensate your gene alteration. If your mutated cells are able to grow independently of external signals and they are immortals you will have a perfect candidate for oncogen. But, even with that, you finally have to prove it in animals.
According to these papers, a single gene is capable of starting a tumor. However, this is the exception, not the rule.
Jan Gronych, Andrey Korshunov, Josephine Bageritz, Till Milde, Manfred Jugold, Dolores Hambardzumyan, Marc Remke, Christian Hartmann, Hendrik Witt, David T.W. Jones, Olaf Witt, Sabine Heiland, Martin Bendszus, Eric C. Holland, Stefan Pfister, Peter Lichter. An activated mutant BRAF kinase domain is sufficient to induce pilocytic astrocytoma in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI44656
Jelinic P1, Mueller JJ1, Olvera N2, Dao F2, Scott SN3, Shah R3, Gao J4, Schultz N4, Gonen M5, Soslow RA3, Berger MF3, Levine DA1. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nat Genet. 2014 May;46(5):424-6. doi: 10.1038/ng.2922. Epub 2014 Mar 23.
I think a short answer is that we do not know. The reports that expression of a gene causes cancer in mice only mean that expressing this gene increases the chance that some normal cells in the transgenic mouse into cancerous cells. In other words, since not all cells expressing the transgene become cancerous, other factors or genes have to be involved. However, we still know too little about cancer to definitively conclude that converting normal cells into cancerous with one gene is impossible.
Regarding the test for cancer cells. Cancer is defined by pathology books as a tumor whose cells invade and metastasize. Hence, I think, you would need to test if the cells you produce invade and metastasize in an animal model.
Hope this is helpful
Thank everybody, I think 2 or 3 gene alteration should be more easy for transformation just like making iPS cells from skin cells through 3 transcription factors overexpression.
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