Extrachromosomal Circular DNA Implicated in Early Development of Cancer
The abnormal generation of circular DNA as a mechanism of cancer, operating by greatly increasing the expression of genes that favor the growth and development of a particular type of cancer. It is a feature of established tumor tissue, but researchers here note that the early presence of extracellular circular DNA in precancerous tissue is a strong marker for the later development of cancer, in that study participants lacking circular DNA in tissue biopsies near all did not go on to develop cancer. The research is focused on one particular tissue and cancer type, but is likely broadly applicable across many varieties of cancer.
Circular DNA, known as extrachromosomal DNA or ecDNA, often harbor cancer-associated genes called oncogenes. Because they can exist in large numbers in a cell, they deliver a super-charged growth signal that can override a cell's natural programming. They also contain genes likely to dampen the immune system's response to a nascent cancer, the researchers found. Previous research had suggested that the circles, which are widespread in human cancers but rarely found in healthy cells, primarily arise in advanced tumors as the abnormal cells increasingly botch the intricate steps required to copy their DNA before each cell division. But the new study shows that the circles can be found even in precancerous cells - and their presence jump-starts a cancerous transformation. Blocking their formation, or their effect on the cells that carry them, might stop cancers from developing, the researchers believe.
The researchers assessed the prevalence of ecDNA, and identified the genes they carried, in biopsies from nearly 300 people with Barrett's esophagus or esophageal cancer, where individual patients were studied as the cancer developed. They found that the prevalence of ecDNA increased from 24% to 43% in early- versus late-stage esophageal cancer, indicating the continual formation of the DNA circles during cancer progression. More tellingly, they found that 33% of people with Barrett's esophagus who developed esophageal cancer had ecDNA in their precancerous cells. In contrast, only one out of 40 people who didn't develop cancer had cells with ecDNA, and that individual passed away due to another cause.
Link: https://med.stanford.edu/news/all-news/2023/04/ecDNA-cancer.html