Cancer DNA Trapping Mechanism Reveals Potential Target for Future Therapies

Rapidly growing, highly metastatic tumors often contain numerous rings of extrachromosomal DNA that carry oncogenes and promote cancer growth. These circular DNA elements have become an important research target for disrupting harmful gene activity. Cancer cells can also contain micronuclei, small structures outside the main nucleus that harbor genetic material. New findings reveal how these structures may help suppress cancer-driving signals, showing that trapping extrachromosomal DNA rings within micronuclei can silence their gene activity.

Max Delbrück Center for Molecular Medicine (Berlin, Germany) researchers, working through the Experimental and Clinical Research Center, a joint institution of Charité—Universitätsmedizin Berlin and Max Delbrück Center, identified micronuclear trapping of extrachromosomal DNA (ecDNA) as a potential target. The study focused on ring-shaped ecDNA that behaves differently from chromosomes during cell division. Instead of orderly chromosomal transport, ecDNA can attach to chromosomes and hitchhike into daughter cells, while less successful rings become trapped in micronuclei.

Using a laser-assisted method developed with the Max Delbrück Center, the team sequenced the genetic material of individual micronuclei. The researchers found that micronuclei are primarily filled with ecDNA, allowing the amount of ecDNA in cancer cells to be estimated by observing visible micronuclei. They also found that the structure of DNA rings changes inside micronuclei, preventing the cell from reading the genes on the rings or translating them into proteins.

In a well-characterized cohort of several hundred patients with neuroblastoma, survival was strongly associated with the presence of micronuclei. Tumor cells with more micronuclei containing large amounts of circular DNA were linked to more successful treatment. The findings were published in Nature Genetics on September 26, 2026, with collaborating institutions including Stanford University and the international Cancer Grand Challenges initiative. The researchers are now investigating ways to prevent DNA rings from hitchhiking into new nuclei during cell division so more rings become trapped in micronuclei.

“The more micronuclei containing large amounts of circular DNA we found in tumor cells, the more successful the patients' treatment was,” said Dr. Anton Henssen, group leader of the Genomic Instability in Pediatric Tumors lab at the Experimental and Clinical Research Center. 

“We found that micronuclei are primarily filled with ecDNA,” says Robin Xu, who is in Henssen's lab and is one of the study's three first authors. "This means we can estimate the amount of ecDNA in cancer cells simply by observing visible micronuclei."

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Max Delbrück Center for Molecular Medicine 
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