How many mutations are there in a cancerous tumor
Kirill Stasevich, "Science and Life"
Cells become cancerous due to accumulating mutations: changes in gene sequences lead to the fact that incorrect proteins are synthesized in the cell, including those that control cell division, and as a result, a malignant tumor is obtained. It is known that there are quite a lot of mutations in cancer cells, and that it is precisely thanks to the mutational diversity that cancer can withstand a variety of treatment regimens. But how much is a lot? Is it really possible to calculate the number of mutations in a tumor, given that its different cells may differ from each other to one degree or another in mutation profile?
Researchers from the University of Chicago Medical Center (Enormous genetic variation may shield tumors from treatment) and the Genomic Institute in Beijing tried to count mutations in a small human liver tumor: its size was about 3.5 cm in diameter, and it numbered more than a billion cells. 300 samples were taken from it for DNA analysis. After the mutations in each of the three hundred zones were counted, the result was extrapolated to the entire tumor, and it turned out that in general there should be about 100,000 (!) DNA damage occurring in the coding regions of genes (that is, those in which information about the amino acid sequence of proteins is encrypted). This value surpassed the most daring calculations – until now it was believed that cancer cells differ from healthy ones by several hundred or several thousand mutational defects (the maximum estimate was only 20,000 mutations). The results of the study are published in the journal Proceedings of the National Academy of Sciences (Ling et al., Extremely high genetic diversity in a single tumor points to the prevalence of non-Darwinian cell evolution, in open access – VM).
Of course, it should be remembered that mutations are distributed unevenly, and most of them occur with a fairly low frequency. The authors themselves say that 99% of different mutations account for less than a hundred cells, and cells with rare genetic defects prefer to be together. Anyway, the new data tell us that there are a lot of mutations in a cancerous tumor "in reserve", in which, obviously, there is no urgent need, which are not under selection pressure, that is, they do not represent a vital need for a cancer cell. The fact that there are mutations useful (for cancer) in tumors, or mutations-drivers that help the tumor grow, and mutations-"passengers" that have no effect on growth and just pass from generation to generation, has been known for quite a long time, but no one could have thought that cancer can have so much genetic diversity.
This is a huge problem for medicine: as we said at the beginning, cancer can survive thanks to mutations that provide resistance to drugs, and with such a huge mutational assortment, it will be quite easy to find the right mutation, some "passenger" mutation will suddenly turn out to be very necessary in changed conditions - for example, when changing the treatment regimen. (Indeed, previous studies have shown that the clinical prognosis worsens with an increase in the genetic diversity of the tumor.) So with anti-cancer therapy, you need to get rid of absolutely all cancer cells as soon as possible and as completely as possible, which is very, very difficult.
On the other hand, let's not forget that in this work only one type of tumor was analyzed, taken from one person. How things are with other types of cancer, of which there are a great many in the world, and how the same variety behaves in the tissues of different people is still unclear. So now it is not necessary to say that each tumor carries 100 thousand mutations – it would be more correct to say that we have learned something new about the limits to which the genetic diversity of cancer can reach. And now we have to understand under what conditions it is worth waiting for these very hundred thousand, and whether it is possible to somehow make it so that there are fewer mutations.
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13.11.2015