Collection of breakdowns
The collection of mutations will serve to fight cancer
Firyuza Yanchilina, "Search"
What role does heredity play in the development of certain diseases? The answer to this extremely important question for our health is being sought by scientific groups of leading research centers. The team of the laboratory "Extreme Biology" of Kazan Federal University under the leadership of Candidate of Biological Sciences Oleg GUSEV studies hereditary gene mutations associated with the development of oncological diseases in different regions of Russia. Scientists have collected the largest collection of gene mutations of patients with hereditary forms of cancer in the CIS and came to the conclusion that there is a relationship between oncomutations in genes and the territory in which the patient lives. Whether this is related to nationality, ethnicity, remains to be seen. There may also be reasons unrelated to genetics: climatic conditions and ecology of the region. The main thing is that the first big step in an important direction has been made. Scientists are going to further develop the project, as they say, both in breadth and depth. Oleg Gusev told "Search" about all this.
– Some people have an increased risk of developing cancer due to genetic characteristics, - says Oleg Alexandrovich. – Hereditary causes account for approximately 9-10% of all cancer cases. The risk of cancer is associated with inherited mutations. A number of genes are known, breakdowns in which cause oncological diseases. In some people, already at birth, such genes are partially damaged. In this case, one of the two copies of the gene (one we get from each parent) carries a pathogenic mutation. Such people are initially healthy, but there is a high probability that the second copy of the gene will break and cancer will develop.
It is very important to understand whether a particular case of cancer is related to hereditary genetics, and exactly where the pathogenic mutation is located in the gene. The choice of treatment strategy depends on this, as well as the interaction of the doctor with the patient's relatives, who may also have an increased risk of cancer. The science of hereditary mutations in malignant diseases is an important field of oncology. Large international associations of scientists are actively conducting serious research.
– How do you study hereditary mutations?
– Russia is a multinational country with a huge territory. And it is very important that the methods of genetic oncodiagnostics, especially concerning hereditary diseases, are reliable and universal. Up to 150 different ethnic groups live in our country, and some of them may have their own genetic characteristics of hereditary cancer. Our task is to study all the variety of mutations, systematize them and use this knowledge to maximize the chance of accurately detecting a pathogenic hereditary mutation associated with cancer in a patient of any nationality. Very often the situation is not obvious, and a number of hereditary mutations can fall under "suspicion".
The genes whose hereditary breakdowns lead to the development of oncology are known. We compiled a list of them and decided not to study individual known mutations in them, but to decipher their sequence completely, taking into account all the features. This maximizes the chance to identify not only known mutations, but also those that were not previously known. To do this, we use special high-performance equipment that allows us to decode entire human genomes.
Then, using special computational methods, we "catch" mutations that meet a number of criteria: they are rare (this is one of the signs that they are associated with the disease), they change the protein so that it can affect its biological properties, and so on.
The initiator and inspirer of this project is the head of the genetic laboratory of the Republican Clinical Oncology Dispensary of the Republic of Tatarstan, Marat Gordievich Gordiev.
– How did you manage to collect the largest database of hereditary mutations in the CIS?
– Thanks to the efforts of our partner doctors, their connections with other dispensaries and, of course, the understanding and support of patients who agreed to participate in the study, we were able to collect a collection by analyzing the blood DNA of more than 1,500 patients with the most common types of cancer, in which the hereditary component is strong: these are breast cancer and ovarian cancer.
Initially, residents of Tatarstan participated in the study, but at later stages we collected data on representatives of other regions of Russia. This was done through a network of contacts of the Kazan Cancer Center with colleagues from similar centers in other regions of Russia. As a result, we collected a database on the genetic profile of patients who, according to all signs (family history of diseases, the appearance of cancer at an early age), had a hereditary predisposition to the development of cancer. And it turned out that no one in Russia or in the CIS had conducted research of this scale before us!
By the way, we have analyzed the complete sequences of more than 100 genes associated with hereditary oncology. Let me remind you what genes and mutations are. A gene is a section of a DNA molecule that encodes a specific protein. Our body consists of proteins. Each gene has a beginning and an end in this DNA molecule, that is, in the genome. Mutations at many points of any gene can lead to bad changes, as the protein product will be disrupted. In the case of our project, we study the entire gene from beginning to end in each patient and compile a list of all mutations in it that can affect the protein product, and therefore be the cause of the disease.
– Does the genome of Russians have any specifics?
– The genomes of Russians are no more specific than the genomes of residents of other parts of our planet. But it is important for us to know which genetic factors (mutations) of an increased risk of cancer are common among residents of Russia. We have proved that the multinational nature of our country is reflected in the spectrum of hereditary mutations associated with cancer.
For example, the spectra of mutations and the frequency of their detection in Tatarstan and in the Western part of Russia are very different. What is the reason? Humanity has been developing for a long time, and different populations of people are geographically isolated. Different mutations could originate in different territories and continue to be present in populations. Then representatives of these groups could move across countries and territories. Accordingly, for example, the indigenous inhabitants of Yakutia or Kamchatka may have a number of hereditary mutations that we are unlikely to meet en masse in other regions.
We have found a number of "suspicious" mutations that have never been described in international databases before (that is, they have signs of cancer development, but there is no complete certainty). It became clear that for a full-fledged reliable diagnosis of hereditary cancer, it is necessary not to use a point analysis of individual mutations, but to study all mutations in cancer-related genes so as not to miss anything.
– Where will the results of your research be used? Will they take medicine to a new level?
– The study of hereditary mutations is of great importance for choosing a specific method of therapy, which is very important for understanding that, for example, in a particular family there is a risk of genetic predisposition to the disease. And this is a signal for healthy relatives to take additional preventive measures, because the detection of cancer in the early stages is the key to successful treatment.
I would not say that our results will take medicine to a new level. Rather, they will allow Russian medicine to approach the international level of genetic diagnosis of cancer. And this is already a huge achievement. For us, scientists, such unique data is a treasure trove for further scientific work on the role of individual mutations and genes in the development of the disease.
The first stage of research has shown that the strategy of studying the genetics of large (more than a thousand) groups of patients with hereditary cancer is an effective approach. A team of doctors, biologists and bioinformatics (these are IT specialists who analyze genomic data using computers and compare them with world databases) is able to conduct an international-level project.
Our plans include "covering" most of Russia with research, as well as working with partners from the CIS, such as Belarus and Kazakhstan. For them, this is also a very urgent problem. It is important to note that the first results showed that it is critically important for the country to implement a genomic project. This will greatly increase the reliability of studies of pathogenic mutations.
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