The cause of cancer cell immortality has been discovered

Pan-Cancer Analysis of Whole Genomes (PCAWG) is a large-scale project to study the genome of cancer tumors. It was completed in early February 2020.  Scientists from 744 scientific institutes have joined together to find out the causes of cancer at the most basic genetic level. In total, the experts studied more than 2,600 tissue samples obtained from biopsies of various tumors: specialists focused on 38 of the most common types of malignant tumors. 

Scientists analyzed not only "working" genes, the function of which was found out in earlier studies, but also the so-called "junk DNA" - fragments of the genome that do not show obvious activity, the role of which remained unclear. Experts were able to establish that changes in these loci can affect the occurrence of mutations leading to cancer. 

Also, experts have studied the cell RNA of cancer cells. This molecule is a matrix that reads information from sections of DNA for subsequent protein synthesis based on the obtained data. This allowed us to understand which fragments of the genome of malignant cells show the greatest activity. 

During the PCAWG project, scientists were able to make several discoveries that allow us to better understand the nature of cancer development. So, it turned out that in the "garbage fragments" of DNA can hide the secret of the immortality of cancer cells – this observation made by scientists during the implementation of the PCAWG project was one of the most striking.

It turned out that mutations in the "sleeping" parts of the genome can lead to the activation of the TERT gene, which affects the synthesis of the telomerase enzyme. It is with a decrease in the concentration of telomerase in cells that shortening of telomere – end sections of chromosomes is associated, which leads to the accumulation of errors in cells. On the one hand, telomerase deficiency leads to cell aging and death, and on the other hand, the mechanism of "turning off" telomerase synthesis allows timely destruction of damaged and mutated cells that pose a danger to the body.

Activation of the TERT gene in cancer cells leads to the fact that the cells do not die even in the presence of various mutations, which becomes the cause of immortality of cells of malignant neoplasms.

It was also found that 95% of malignant tumor cells contain so-called "driver mutations" - the result of DNA copying errors during cell division. On average, there are 4-5 such mutations in cancer cells that give cancer cells an advantage over healthy ones. Also, a whole avalanche of genomic rearrangements – "genomic catastrophes" - is detected in 18-22% of cancer cells. This is the result of multiple breaks of the DNA molecule and subsequent random crosslinking, resulting in the cell's genome begins to resemble a"salad".

Overall, the global research project on the cancer genome helped to understand: there is no single mechanism for the development of malignant tumors and, consequently, it is not possible to develop a universal method for preventing and treating cancer. Scientists believe that the secret of success is only in a thorough study of each type of malignant neoplasms, the features of their development, and the response to treatment. 

Feb. 10, 2020, 11:59 a.m.

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