What mutations lead to lung cancer in non-smokers?
Geneticists have dealt with lung cancer in non-smokers
At the same time, chemotherapeutic drugs are toxic and not only kill the tumor, but also damage healthy tissues and organs. Scientists are developing methods of pinpoint strikes, the so-called targeted therapy aimed exclusively at cancer cells.
For targeted therapy, it is very important to know exactly which disorders at the level of genes, RNA and proteins occur in tumors of one kind or another, and there are many of them, which mutations occur in DNA and what changes they lead to in the cell. Practical doctors pin their hopes on molecular geneticists who are trying to understand the picture of mutations and biochemical changes of each specific type of malignant tumors.
Scientists have joined the international consortium The Cancer Genome Atlas Research Network to, as the name suggests, create a genetic atlas of cancer.
The Cancer Genome Atlas (TCGA) project is coordinated by the National Cancer Institute and the National Human Genome Research Institute. The Cancer Genome Atlas Research Network consortium brings together molecular geneticists, bioinformatics and clinicians from more than 50 scientific institutions.
"Newspaper.Ru" has already written about the results of the first stage of work on the study of the molecular picture of different tumors, which were published in September 2013 in 18 articles in Nature. The work continues. The study, published in the latest issue of Nature (Comprehensive molecular profiling of lung adenocarcinoma), was also attended by a Russian doctor and scientist Fedor Moiseenko, an employee of the St. Petersburg Academic University and the Scientific and Practical Oncology Center. The study is devoted to the molecular picture of lung adenocarcinoma.
As Fyodor Moiseenko explained to the Newspaper.En", adenocarcinoma is one of the types of lung cancer that is mainly not associated with smoking. Lung cancer ranks first in mortality in the world, and smoking is the main risk factor for this disease. But in North America and Western Europe, smoking has been reduced by a quarter over the past 20 years. In these countries, adenocarcinoma is the most common, which can happen even in non-smokers (according to medical criteria, these include those who have smoked less than 100 cigarettes in a lifetime). As for Russia, adenocarcinomas account for about 20% of all lung tumors in men and 35% in women, and squamous cell lung cancer is in the first place among Russians. In terms of aggressiveness, both types of cancer are about the same.
The work showed, says Fedor Moiseenko, that despite the similar course of the disease in different patients with lung adenocarcinoma, their tumors may have completely different sensitivity to medications, including those that are considered targeted.
The scientists were faced with the task not just to identify the mutation, but to show that it is critical for this tumor and that if it is blocked with a drug, it will stop the growth of the tumor.
To solve this problem, experts described the molecular profile (that is, changes at the molecular level) of 230 different tumors. To do this, they used almost all currently existing methods of genetic analysis. In the same tumor tissue samples, they sequenced (determined the sequence of "letters") DNA, counted the number of copies of various genes, analyzed mRNA (transmitting information from DNA to build proteins) and microRNA (small RNA molecules playing a regulatory role), analyzed proteins and evaluated chemical changes in DNA called methylation (when methyl groups –CH 3) are attached to the DNA molecule.
The researchers were able to identify driver mutations, that is, those that triggered the malignant process, led to the appearance of features characteristic of tumor cells in normal cells.
It turned out that driver mutations occur in a larger proportion of tumors (76%) than previously thought (62%). The most frequently mutated genes whose association with lung cancer was already known earlier (EGFR gene, for example), but were also described for the first time (for example, MGA). Interestingly, some genes were more likely to mutate in women, and others in men. Thus, scientists have made significant progress in describing the picture of molecular changes in lung adenocarcinoma.
The results obtained will tell practical doctors exactly how to treat a patient based on the genetic characteristics of his tumor, which targeted drugs to use so that they act on what is needed.
According to Fyodor Moiseenko, lung cancer and tumor mutations are the sphere of his long–standing scientific interest and these studies are actively developing at the St. Petersburg Academic University - the scientific and Educational Center for Nanotechnology of the Russian Academy of Sciences. Although this work mainly used the practical experience of Russians in the treatment of this type of tumors, and high-tech methods were used by Western researchers.
Portal "Eternal youth" http://vechnayamolodost.ru11.07.2014