It has long been known how cancer develops: for a cell to become malignant, mutations must gradually accumulate in several key genes. The mutations cause these genes to be deregulated, i.e. produce abnormal proteins, and the cell then begins to behave in a chaotic and dangerous way for the organism, multiplying without stopping. These mutations are permanent changes in the DNA sequence that alter the genetic information it contains. Thus, the only things that cause cancer are those that can damage DNA, such as ultraviolet radiation, or toxic chemicals such as those found in tobacco. A recent article published in nature It casts doubt on this universally accepted dogma, and shows, for the first time, that tumors can also form without the need for mutations, at least in flies.
As multicellular organisms, we have a problem: each of our cells must follow a fixed routine and perform precisely the functions assigned to it if we are to survive. The genetic program they have stored inside them is the guarantee that this will be the case. All would be well if time and opportunity did not allow the instructions contained in these basic guides to deteriorate, like a book that becomes unreadable when the ink wears out. Fortunately, we have systems in place to correct these errors, and if that were not enough, there are ways to destroy cells with defective genes so that they no longer pose a threat. But every now and then someone escapes the control mechanisms and goes ahead and alters their DNA, with potentially disastrous consequences. This is the only recipe for cancer… or so it was thought.
The role of epigenetic changes
The group led by Dr Martinez and Dr Cavalli, both from the University of Montpellier, has turned this idea on its head with a study on the fruit fly, the famous fruit fly, which is widely used in biology experiments. To better understand the formation of cancer, the scientists investigated the effects of epigenetic changes on this process. These are a series of chemical modifications to the DNA molecule that do not change the genetic information itself, but how it is read. Epigenetic modifications, which contribute to disease by turning genes on and off, are known to accumulate in cancers, as in many other processes, but it was not thought that this was sufficient to form a tumor.
Scientists genetically modified the flies so that they do not make certain proteins. Polycombwhich is responsible for making epigenetic modifications throughout the genome. In this way, a group of genes is usually silenced thanks to the control of genes. Polycombthey turned out to be unexpectedly active, including some that are usually seen working more than expected in cancers, such as those in the JAK-STAT family. Surprisingly, this was enough to cause tumors in flies in the absence of mutations, something that had never been seen before. If flies were made to produce them again, Polycomb Once tumors formed, they did not regress, indicating that the process initiated by changes in epigenetic patterns was irreversible.
Proteins Polycomb Not only is it an important part of organizing genetic information in insects, but it is also found in mammals, suggesting that this may also occur in humans. In fact, problems have already been seen in Polycomb In some cancers, but it was thought to be a secondary process. The paper suggests that it may play a more important role in tumor formation than previously thought.
Not just irreversible changes in genes
These experiments do not call into question everything we have learned about the genesis of cancer: the explanation for the abnormal behavior of the cancer cell that gives rise to everything and its offspring remains that a number of important genes are not doing the work they are supposed to do. The difference is that this editing does not seem to require permanent changes to the genes, as previously thought, but reversible chemical modifications to the DNA may be sufficient to achieve the same effect. It will now be necessary to know whether this happens spontaneously in humans.
That genetic modifications play a role in our cancers is not new, but until now they have not been seen in the absence of mutations, perhaps because they have not been looked for well enough, or perhaps because mutations eventually appear anyway, even if they are not necessary to start the process. This may happen because the genome of a mutated cell ends up being unstable, which encourages the emergence of mutations sooner or later. In any case, the epigenetics of cancer is gaining greater importance after this study, which is likely to stimulate current research into the anti-tumor effects of drugs that can reverse chemical modifications to DNA.
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