Diagnosis of cancer by fragments of chromosomes

Alexandra Bruter, <url> 

A new way to diagnose oncological diseases was accidentally discovered by obstetricians and gynecologists from Boston. They told about it at the international conference on prenatal diagnostics, held in Washington.

In recent years, non-invasive methods of diagnosing congenital, especially genetic diseases in the fetus, have been actively developing. Until now, ultrasound helped to suspect fetal abnormalities – not a very accurate method, the reliability of the results of which strongly depends on the skills of the doctor conducting the study. To confirm or refute suspicions that have arisen during ultrasound, doctors usually recommend invasive procedures: amniocentesis or cordocentesis. They are a puncture in order to obtain several milliliters of amniotic fluid or umbilical cord blood for analysis. There is always a small number of cells in the amniotic fluid and in the umbilical cord blood, the karyotype of which can be examined and understand whether there are chromosomal abnormalities in them that cause congenital diseases, for example, Down syndrome. Being invasive, these procedures are quite dangerous, they are associated with a 0.5-1% risk of termination of pregnancy, and pregnant women often go to them reluctantly.

Developing sequencing technologies are helping to replace invasive procedures with non-invasive ones. It turned out that fetal DNA gets into the mother's blood and can be isolated from there. Around the seventh week of pregnancy, fetal DNA appears in the mother's blood, and two hours after delivery disappears. The standard procedure for isolating such DNA was developed in 2007 and was based on the fact that fetal DNA is present in the bloodstream in the form of smaller fragments than the mother's own DNA.

By isolating the DNA of the fetus, you can learn quite different things about it. By the presence of fragments of the Y chromosome, it is possible to determine the sex of the unborn child. This is important if there is a genetic disease linked to the X chromosome in the mother's family (such as hemophilia, which women rarely suffer from, but may be carriers of a mutant gene). Some companies (for example, Natera) already offer non-invasive paternity tests that work starting from the ninth week of pregnancy.

From a medical point of view, fetal DNA-based methods of searching for congenital diseases are of greater interest. First of all, these can be monogenic diseases (caused by a mutation in a single gene). But there are a lot of such diseases, and the search makes sense only if it is necessary to check whether a disease that has already been encountered in the family has been transmitted to the child, or the task is to exclude several of the most frequent diseases in this population.

But by isolating fetal DNA from the mother's blood, you can count the number of chromosomes in each pair, and make sure whether they are a pair. Most trisomies (three chromosomes instead of two) are lethal, and the fetus does not survive until birth. The exceptions are sex chromosomes and three autosomes: 13, 18 and 21. It is noteworthy that these three chromosomes contain fewer genes than any other non-sex chromosome. Trisomy on the 21st chromosome causes a well-known Down syndrome, with which you can live for quite a long time and sometimes relatively successfully. Two other trisomies, Patau syndrome (chromosome 13) and Edwards syndrome (chromosome 18), although they allow a child to be born, are associated with very severe abnormalities and high mortality at an early age. If the number of sex chromosomes differs from two, then this is usually due to non-life-threatening and even not always well-visible abnormalities, but, as a rule, leads to infertility (except for variant XXX).

Patau syndrome and Edwards syndrome (and to some extent Down syndrome) are indications for termination of pregnancy – the earlier, the better. Therefore, a reliable and safe method capable of detecting these pathologies at an early stage is very important. This is exactly what the study of fetal DNA contained in the mother's blood is. The method has become routine in the UK and some US states. You can read about the application of this method in an interview published earlier with Egor Prokhorchuk, head of the Laboratory of Genomics and Epigenomics of Vertebrates at the Bioengineering Center of the Russian Academy of Sciences.

A fairly large amount of data has accumulated during the use of the use. It turned out that in some women, the test shows aneuploidy (an odd number of chromosomes) in the fetus for some one (sometimes more) chromosome, but then it turns out that the fetus is completely healthy. In addition to a certain percentage of really mistakes, there were much more women with cancer in this group than one would assume. They did not know about their illness – the early stages are often relatively asymptomatic.

Malignant cells are characterized by chromosomal instability, aneuploidy on a variety of chromosomes in them is a frequent occurrence. Due to the anti-cancer mechanisms built into the human genome, such cells often die, and, probably, their DNA ends up in the bloodstream in the form of relatively short fragments. The authors of the report analyzed approximately 125 thousand samples, of which the analysis showed aneuploidy in about four thousand patients. Ten of them turned out to have cancer, most of the others actually had fetal abnormalities. Out of 39 patients with aneuploidy on several chromosomes, seven were ill with cancer. One of the patients managed to take blood for analysis after recovery – the analysis no longer showed aneuploidy.

Probably, by choosing a more suitable technology for extracting extracellular DNA from the blood, you can try to create a simple, cheap and accurate method for finding cancer that does not manifest itself.

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15.07.2015