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Pinpointing a reason

For the current study, researchers turned to a specific example of cancer development people with a condition known as Barretts esophagus, which occurs when the cells lining the lower part of the esophagus are damaged by acid reflux and become more like cells lining the intestine than healthy esophageal tissue. About 1% of these people develop esophageal cancer, which is difficult to treat and has a high mortality rate. Because the outcome is so poor, people with Barretts esophagus are routinely monitored with endoscopies and biopsies of the abnormal tissue. Because of these frequent biopsies, the researchers had access to tissue samples collected both before and after cancers developed.

The researchers assessed the prevalence of ecDNA, and identified the genes they carried, in biopsies from nearly 300 people with Barretts esophagus or esophageal cancer treated at the University of Cambridge or at Seattles Fred Hutchison Cancer Center, 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 Barretts esophagus who developed esophageal cancer had ecDNA in their precancerous cells. In contrast, only one out of 40 people who didnt develop cancer had cells with ecDNA, and that individual passed away due to another cause.

Others senior researchers on the study include Stanford University'sMischeland Howard Chang, MD, PhD, professor of genetics and the Virginia and D.K. Ludwig Professor in Cancer Research; senior staff scientist Thomas Paulson, PhD, from Seattles Fred Hutchison Cancer Center; assistant professor of pediatrics Sihan Wu, PhD, from the Childrens Medical Center Research Institute at the University of Texas Southwestern Medical Center; and professor of cancer prevention and director of the Early Cancer Institute Rebecca Fitzgerald, MD, from the University of Cambridge.

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UC San Diego Researchers Help Discover That Tiny DNA Circles ... - University of California San Diego