Cancer is protected by chromotrypsis
Destroyed chromosomes make cancer cells resistant to drugs
Tatiana Matveeva, "Scientific Russia"
Researchers from the University of California (USA) have found that the phenomenon of chromotripsis leads to the rearrangement of genomes and extra-chromosomal DNA, which helps cancer cells not only resist treatment, but also become more aggressive, the press service of the university reports.
The results of the study are published in the journal Nature (Shoshani et al., (Chromothripsis drives the evolution of gene amplification in cancer) – VM.
In their article, the authors describe how a phenomenon known as chromotripsis destroys chromosomes, which are then reassembled, which ultimately promotes the growth of cancer cells.
Chromotripsis is a mutational process of a cell, during which a massive rearrangement of its genome occurs. And genomic rearrangement is a key characteristic of many cancers, allowing mutated cells to grow faster without succumbing to anti–cancer therapy.
During chromotripsis, the chromosome in the cell is divided into many parts, in some cases into hundreds, and then reassembled, but in a mixed order. Some parts are lost, while others are preserved as extra-chromosomal DNA (vcDNA). Some of these elements of vcDNA contribute to the growth of cancer cells and the formation of chromosomes of the smallest size.
Earlier, a study by scientists from the University of California showed that up to half of all cancer cells in many types of cancer contain vcDNA carrying genes that contribute to the development of cancer. Now the team has sequenced the complete genomes of cells that develop resistance to drugs, and found that the destruction of chromosomes leads to the formation of genes carrying vcDNA, which confer resistance to anti-cancer therapy.
Scientists have also determined how chromotripsis controls the formation of vcDNA after amplification (copying) of the gene inside the chromosome.
"Chromotrypsis converts intra-chromosomal amplifications into extra-chromosomal amplifications, and this copied vcDNA can then combine into chromosomal regions in response to DNA damage as a result of chemotherapy or radiation therapy," said Ofer Shoshani, first author of the study, professor of medicine, neurobiology, cellular and molecular medicine at the University of California San Diego School of Medicine. "The new work highlights the role of chromotripsis at all critical stages of the life cycle of amplified DNA in cancer cells, explaining how cancer cells can become more aggressive or resistant to drugs."
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