In a study reported in Nature Genetics in August, Ludwig San Diego’s Paul Mischel and colleagues showed that the amplification of cancer genes located on free-floating circles of DNA in the nucleus, or extrachromosomal DNA (ecDNA), is associated with poor patient outcomes across multiple types of cancer. Paul and his colleagues have previously shown that ecDNA is hardly ever seen in healthy cells and is associated with accelerated tumor evolution and high cellular heterogeneity in tumors, which often drive drug resistance. But it wasn’t entirely clear how common ecDNA is across cancer types and what its clinical impact might be. Paul and his team found that ecDNA occurs at minimum in 14% of human tumors, and much more frequently in the most malignant forms of cancer, such as the brain cancer glioblastoma, sarcoma, and esophageal, ovarian, lung, bladder, head and neck and gastric cancers. The ecDNAs were found to be significantly enriched for oncogenes. Patients with ecDNA amplification have significantly worse five-year survival outcomes than those without, so strategies that target ecDNA for cancer therapy could yield significant dividends. Paul is co-founder of a startup, Boundless Bio, that plans to develop such therapies.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).