Oncogenes & Ontology
Someone recently said to me that telomerase wasn’t oncogenic. And in one sense, they were exactly right: the gene that produces telomerase is not recognized as an oncogene. In the other sense however, they were wrong: the reactivation of telomerase (or ALT) is a necessary step in the route to a malignant neoplasm, known as oncogenesis. This is one of the reasons I have never liked the “oncogene” designation. It’s fuzzy and a little misleading. Moreover, I think this fuzzyness is related to some of our misconceptions about cancer.
When we look at disease, we tend to look at it in terms of cause and effect. E.g. influenza causes flu, pneumocystis causes pneumonia, etc. And this schema works really well when you a are dealing with pathogens. Charge in, antibiotics and antivirals blazing, remove the cause, and the disease goes away (usually, although if it doesn’t then you probably have just not removed the cause well enough, as is the case with latent HIV). However, cancer and genetic diseases are often a different story. People ask: “Why haven’t we cured cancer yet?” and I have seen at least one paranoid documentary claiming we could obviously cure cancer at any time and just don’t because evil corporations profit off of it. Ideas like these are the result of the misconception that cancer has simple causes and simple solutions.
Misconception concerning oncogenes is a primary culprit in the current confusion, and (as I talked about in an older post) why we tend to hear a lot these days about “the X cancer gene”. These ideas are absurd. There are two mistakes working together here: (1) That oncogenes are genes whose only purpose is to cause cancer; (2) That oncogenes are sufficient to cause cancer.
(1) In truth, oncogenes have a variety of roles in the body, it is their constitutive over-expression that drives the growth component of cancer. Many oncogenes are lethal if knocked out, which is to say they are vital to development and survival of the whole organism. It is just that there is actually to much of a good thing.
(2) This is where things really begin to go off the rails. An oncogene alone is no more a cause of cancer than active telomerase or the lack of a tumor suppression gene. The development of a neoplasm is a stepwise process and no one step is sufficient while all of them are necessary. Generally it requires three mutations for a benign neoplasm and five for a malignant one (certain conditions, like a genetic predisposition for retinoblastoma or infections with an oncovirus take this number down by one). And while these mutations need to perform similar functions (cause growth, remove reproduction limits, direct angiogenesis, alter metabolism, etc), they can occur in any of a multitude of individual genes.
With a system so complex, it should be apparent why the old schema doesn’t work. There is no one single cause of cancer and no one single cure. There is no one “X cancer gene”. Cancer is a large spectrum of conditions the battle against which will rage on well into the future. While we might find ways to cure specific cases and deal with specific oncoviruses and genetic predispositions we will never cure ‘cancer’. To do so would mean to remove all mutation and make ourselves essentially genetically static. I hope I don’t have to explain why that would be a bad thing.
Sources & Further Readings
- I don’t really have a whole lot on oncogenes lying around at the moment, but a nice place to get an introduction might be Geoffrey M. Cooper’s textbook on the subject. It’s short and pretty straightforward.