27 May 2019

Tumor DNA in urine analysis

Scientists from Moscow State University have created a system for early diagnosis of bladder cancer

RIA News

Russian and foreign molecular biologists have created a very simple and effective test that allows you to find traces of bladder cancer at the earliest stages of its development. Its description and the first results of its use were presented in the journal EBioMedicine (Avogbe et al., Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer).

"I have been studying how telomerase proteins work for many years. Therefore, my participation in the project of the International Agency for Research on Cancer became a logical continuation of my work at Moscow State University. Now we want to improve the methodology for determining mutations in TERT and make it even simpler and cheaper," said Maria Zvereva, a chemist from Moscow State University.

Cancer tumors, germ cells and stem cells are virtually immortal from the point of view of biology – they can live almost indefinitely in an adequate habitat, and divide an unlimited number of times. In contrast, normal adult body cells gradually lose their ability to divide after 40-50 division cycles, entering the aging phase, which presumably reduces the chances of developing cancer.

These differences are due to the fact that each division of "adult" cells leads to a reduction in the length of their chromosomes, the end sections of which are marked with special repeating segments, the so-called telomeres. When there are too few of them, the cell retires and ceases to participate in the life of the organism.

In embryonic and cancer cells, this never happens, since the end sections of their chromosomes are updated and lengthened with each division due to special enzymes-telomerases. The genes responsible for the assembly of these proteins are "turned off" in adult cells, as a result of which their telomeres do not lengthen. With the development of a tumor, these sections of DNA are activated and help it grow indefinitely.

Zvereva and her colleagues from Portugal and France found out that this feature of cancer cells can be used for very fast and cheap detection of even the most inconspicuous traces of tumors in the genitourinary system.

Analyzing the composition of urine, blood and tumors of several dozen Frenchmen suffering from bladder cancer, scientists found that a fairly large number of DNA fragments from dead tumor cells fall into their secretions. These fragments, as scientists have noticed, often contain fragments of the TERT gene, one of the main conductors of telomerase activity.

A few years ago, molecular biologists noticed that the development of bladder cancer is almost always accompanied by the appearance of two mutations in the key part of this gene that controls its activity. This prompted Zvereva and her associates to think that a similar property of the mutant version of TERT could be used for early cancer diagnosis.

Guided by this idea, scientists created a simple, but at the same time reliable diagnostic complex that found DNA fragments with the "right" part of this gene in blood, urine or tissue samples, multiplied it in the presence of mutations and notified doctors about it.

As the tests of this test have shown, it is able to find traces of cancer even if for every dead tumor cell there are several hundred healthy ones whose DNA got into the biological materials being studied. In this respect, it is significantly superior to existing diagnostic systems and does not require painful and potentially dangerous operations.

At the same time, this diagnostic system does not require any special equipment and reagents, and it can be implemented in any clinical laboratory where there are basic tools for DNA analysis. All this, as scientists conclude, allows us to hope that she will enter medical practice very quickly.

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