Experts have defined Chromothripsis as chromosome shattering. They have said that chromosomes, which go through Chromothripsis, are first separated into many pieces and then are sewn back together in random order by DNA repair process most probably non-homologous end-joining. In the new study, scientists from the University Of California San Diego School Of Medicine and the UC San Diego branch of the Ludwig Institute for Cancer Research have shown how Chromothripsis helps in the growth of cancer cells. The findings of the study show that Chromothripsis forces gene amplification in cancer. The findings of the research have been reported in the journal called Nature. Chromothripsis is a mutational process in which up to thousands of clumped chromosomal reshuffles takes place in a single episode in limited genomic areas in one or a few chromosomes. Chromothripsis is linked to both cancer and congenital diseases, said the experts. The author of the study has said that these shuffles happen only in one-step. In this process, a chromosome is divided into hundreds of parts and again rearranged in random order.
Experts have said that during the process, some pieces of the chromosome are lost while some pieces remain as Extra-Chromosomal DNA (ecDNA). This ecDNA trigger the growth of cancer cells. They form minute sized chromosomes called ‘double minutes’. Many past studies have shown that up to half of all cancer cells in various types of cancer carry ecDNA, which have the cancer-triggering gene. In this recent study, scientists have applied direct visualization of chromosome formation to find out the steps of gene amplification. They have tried to observe the method of an underlying resistance to methotrexate as well in the study. The group of scientists has created a sequence of entire genomes of cells, which have drug resistance. It has been found that chromosome shattering triggers the formation of ecDNA, which carries genes that forces anticancer therapy resistance. Scientists have shown how Chromothripsis prompts the growth of ecDNA after gene amplification inside a chromosome.
The findings of the study have confirmed that Chromothripsis is the main driver, which speeds up genomic DNA reshuffle and magnification into ecDNA. It allows for faster acquisition of lenience to changed growth conditions. Chromosome shattering changes intrachromosomal amplification into extra-chromosomal amplification. This magnified ecDNA further add into chromosomal sites in response to DNA harm caused by chemotherapy or radiation. The study shows the role of Chromothripsis at all vital stages in the life cycle of magnified ecDNA in cancer cells. The study explains how cancer cells turn more hostile to cancer therapies. The findings of the study have clearly shown that repetitive chromosome shattering can lead to anticancer drug resistance. Scientists have identified DNA repair pathways as well, which are crucial for rearranging the shattered pieces of chromosomes. It allows the rational design of combination drug treatments to stop the growth of drug resistance in cancer patients. It improves the outcome of the treatment as well, said the experts. Dr. Ofer Shoshani from UC San Diego School of Medicine has led the new study.