An international collaboration of scientists has uncovered how circular fragments of DNA, known as extrachromosomal DNA (ecDNA), act as early and powerful drivers of glioblastoma, the most common and aggressive adult brain cancer.
The study, published in Cancer Discovery, reveals that ecDNA rings carrying cancer-causing genes often arise during the earliest stages of tumor development—sometimes even before glioblastoma fully forms. These early events appear to fuel the tumor’s rapid growth, adaptability, and resistance to treatment.
Led by Dr. Benjamin Werner (Queen Mary University of London), Professor Paul Mischel (Stanford University), and Professor Charlie Swanton (The Francis Crick Institute), the team analyzed genomic and imaging data from glioblastoma patients and applied computational modeling to reconstruct the evolutionary history of ecDNA. Their analysis showed that ecDNA often harbors EGFR, a potent oncogene, and its aggressive variant EGFRvIII.
The findings suggest a possible “window of opportunity” for early detection. If tests can identify EGFR ecDNA in patients—potentially through blood-based diagnostics—therapies could be administered before the cancer develops resistance.
The work highlights ecDNA as a crucial force in tumor evolution and points to its potential as a biomarker for diagnosis and treatment strategies across multiple cancer types.
