Revelation! Why is chromosomal DNA most common in human cancer and can lead to poor prognostication in cancer patients?

August 25, 2020 // -- In a recent study published in the international journal Nature Genetics entitled "Extrachromosomal DNA is associated with oncogene amplification and poor outcomes multiple levels of cancer", scientists from the University of California and other institutions have found that proliferation of specific genes in DNA outside the chromosome may induce cancer and lead to poor prognostication in patients with multiple types of cancer.
the study, researchers found for the first time that amplification of a gene called ecDNA cancer (the proliferation of extrachromosome DNA) is widespread in a variety of cancer tumor types; At least 14 percent of human tumors occur, and they occur much more frequently in the most malignant cancers, including glioblastoma, sarcoma, esophageal cancer, etc., and the structure of this study shows that ecDNA plays a key role in the development of cancer.
Photo Source: Paul Mischel, UC San Diego researcher Michel said: 'We found that patients with ecDNA in cancer had significantly shorter survival times than other cancer patients, and that tumors in these patients' bodies were driven by other molecular mutations, even by tumor type.
The shortening of the overall survival of patients also suggests that cancer patients with ecDNA-driven tumors are not responding well to current treatments, which may require new treatments, and that research may help scientists develop potential anti-cancer therapies to treat ecDNA-driven cancer patients.
This study provides a new window into the molecular epidemiology of ecDNA in cancer and a new opportunity for longitudinal studies of why patients are not responding well to therapy; researchers have observed that ecDNA amplification occurs in many types of cancer but is not in normal tissue or whole blood, and that the most common relapse gene amplification Often in ecDNA, it's worth noting that the researchers found circulatory markers based on ecDNA amplification in 25 of the 29 cancer types analyzed, as well as a higher frequency of cancers of the most invasive tissue types, including glioblastoma, sarcoma, and esophageal cancer.
researcher Michelle points out that cancer seems to be playing an old evolutionary trick, in which cancer genes and the regulatory regions around them are freed from the constraints of the chromosomes to which they belong, driving higher copies of cancer genes, accelerating tumor evolution, promoting cancer cell resistance to therapy, and giving tumors the ability to rapidly change the cell genome to react to rapid changes in the environment, ultimately accelerating tumor evolution and driving their resistance to therapy. In the
paper, the researchers performed intensive computational analysis of genome-wide sequence data from more than 3,200 tumor samples from the Cancer Genome Mapping Program (TCGA) and the Genome-wide Pan-Cancer Analysis Program (PCAWG), analyzing more than 400 TB of raw sequencing data and observing the effects of ecDNA amplification on the prognostic effects of cancer patients. In the
article, researchers developed a powerful computer technology called Amplicon Architect that identifies ecDNA based on three key characteristics, including circulatory, high copy count, and break point reuse;
Chromosome DNA (ecDNA) is a unique ring-like DNA that contains functional genes located outside the cell chromosome and can replicate itself; ecDNA replicates quickly in cancer cells, inducing a higher number of copies of cancer genes, and this feature is passed on to child cells in an asymmetrical manner during cell division, allowing cancer cells to increase or lower the expression of cancer genes on ecDNA. Ensuring that cancer cells survive in selective stress environments, including chemotherapy, targeted therapy, immunotherapy, or chemotherapy, also makes ecDNA one of the main mechanisms of cancer recurrence and resistance to therapy, which is rare in healthy cells but is often found in a variety of solid tumors and is the main driver of most malignant and difficult cancers, especially those characterized by high copy amplification of cancer genes.
() References: 1 Extrachromosomal DNA is common in human cancer and drives poor patient outcomes 2 Kim, H., Nguyen, N., Turner, K. et al. Extrachromosomal DNA is associated with oncogene amplification and poor outcomes across multiple cancers. Nat Genet (2020). doi:10.1038/s41588-020-0678-2.