Cienciaes.com: We are ever-growing cellular mosaics.

2019-07-14 19:41:13

One of the aspects of scientific research that seems most unfair to me is the discrimination that exists between disciplines when it comes to financing their activity. While dedicating billions of dollars or euros to pure Physics, to understand, for example, the origin of energy or dark matter in the universe, is possible without the need to make great promises to Humanity, research in pure Biology is scarcely financed and it is necessary, in general, to promise advances against diseases to obtain adequate financing.

Fortunately, research on diseases has made it possible to make important advances in fundamental science, and cancer is perhaps the disease whose research has contributed the most pure knowledge to Biology. Studying how it is generated and how it progresses has revealed a myriad of genes and mechanisms involved in the normal life of cells. Research has also made it clear that cancer occurs thanks to the generation of a cell clone derived from an original cell, which has undergone mutations in certain genes that control cell division.

How have these mutations occurred and why? Until very recently it was believed that the cells of an organ or tissue are all identical, except for some that, due to some type of aggression, be it chemical by some harmful substance, or physical, such as ultraviolet rays from the sun, have undergone mutations that They can turn them into tumors. It is these different cells that can eventually lead to cancer.

This idea seemed reasonable, since all cells in an organ derive from stem cells that, in principle, do not contain mutations. However, we already know that in science it is not possible to settle for what appears to be common sense. If it had been done that way, quantum mechanics and relativity would never have been discovered. No, common sense only serves to develop apparently reasonable ideas that later need to be checked by confronting reality.

This is not always easy or possible, because, sometimes, to confront an idea with reality it is necessary to wait for a technology to be developed that makes this confrontation possible. In the case at hand, to check if all the cells of an organ are genetically identical, it would be necessary to separate them, analyze the genome, or at least a significant part of it, of thousands of them, and compare these genomes among the various cells analyzed. looking for potential differences. As we can undoubtedly imagine, it would be a tedious job that would require very powerful tools for obtaining and analyzing genomic data.

numerous mutations

Of course, one does not start doing this type of very expensive analysis without some previous data that suggests that it can be fruitful. Previous data in this sense had been obtained thanks to the genetic analysis of various types of cancers and their comparison with the genomes of the normal cells from which the cancers derive. The data obtained indicated that the mutations found in the tumors were also found in many apparently healthy cells or, at least, had not yet become tumor cells.

Considering these data, a group of researchers from several American universities uses the sequencing technology of ARNdo not give ADN, to analyze the possible mutations accumulated in the healthy tissues of five hundred people. He ARN It is a nucleic acid of which multiple copies are generated as a result of the functioning of the genes, copies that have an identical sequence of letters to theirs. Since there are hundreds of copies of this ARN corresponding to each gene that functions in a given cell, this facilitates the sequencing and detection of mutations even in only a few cells.

In this way, scientists obtain proof that at least 29 different tissues and organs in the body are made up of cells that have mutated throughout life and that have reproduced, transmitting the mutations to daughter cells. This indicates that each tissue is like a mosaic, made up of a set of cell clones, each with several different mutations. Some of those mutations could, in effect, lead to at least one cell in one of the clones becoming cancerous.

The organism is thus revealed as a mosaic of cell clones of different sizes and with different mutations. It is a living mosaic, of course, with many of the pieces increasing and growing throughout life, as cells reproduce and mutate as a consequence, and as different environmental insults induce mutations. here and there in the genome.

33% of the analyzed clones contained at least one mutation that increased the probability of leading to cancer. Clones made up of a greater number of cells are the ones that can more easily cause cancer, since it is more likely that one of the mutated cells will mutate further and become a tumor. Fortunately, large clones were not frequent, but even so, clones with more than 30,000 cells, already considered large, accounted for 5% of the detected loess.

The scientists also discover that, as expected, the number of clones and the number of mutations increases with age and towards the end of life each human being is a huge cell mosaic, particularly in the skin and in the esophagus, two organs with a high cell reproduction and that are exposed to external aggressions from the environment. Both factors combine to increase the probability of cancer.

These studies open up the possibility of developing methods to determine very precisely the risk of cancer in different people, as well as to detect it very early, which will make it possible to defeat it more frequently. The advance against cancer continues inexorably.

Reference:

Keren Yizhak et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364, eaaw0726 (2019).

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