Scientists from the United States and the United Kingdom have confirmed for the first time that extracellular mutant DNA (ecDNA) circulating outside chromosomes promotes malignant brain tumors. This discovery has been evaluated as a potential clue for detecting and treating brain tumors much earlier.
Researchers from Queen Mary University of London and the Francis Crick Institute in the United Kingdom, along with Stanford University in the United States, noted on the 8th (local time) that "ecDNA appears before cancer cells are formed, accelerating tumor growth and hindering treatment," and published their findings in the journal Cancer Discovery.
ecDNA is a small DNA fragment that floats in a circular shape outside chromosomes, carrying genes that promote cancer and multiplying rapidly. As a result, tumors grow faster and treatment is hindered. It has been found not only in glioblastoma, a malignant brain tumor, but also in various cancers such as neuroblastoma in children and lung and stomach cancer in adults, playing a significant role in both adult and pediatric cancers.
The exact working mechanism of this ecDNA inside the body has not been clearly understood yet, largely due to the challenges in conducting the research. The Cancer Grand Challenges, a cancer research organization jointly established by Cancer Research UK and the U.S. National Cancer Institute (NCI), has also identified ecDNA as one of the most difficult problems to solve in cancer research. This current study was also conducted with the support of this organization.
The research team conducted a detailed analysis of patient genomic and imaging data and found that most ecDNA contains the potent cancer gene "epidermal growth factor receptor (EGFR)." In some patients, EGFR mutations were observed even before cancer cells were formed, making the tumors more aggressive.
EGFR plays a role in promoting cell growth and division in brain cells. When amplified within ecDNA, it has been shown to rapidly promote malignant brain tumors such as glioblastoma and increase resistance to treatment.
EGFR particularly plays a role in promoting cell growth and division in brain cells, and when amplified within ecDNA, it has been shown to rapidly promote malignant brain tumors such as glioblastoma and increase resistance to treatment.
Dr. Benjamin Werner, the lead researcher from Queen Mary University of London, said, "We analyzed various points around the tumor, reconstructing the evolution of cancer as if we were conducting an archaeological dig," and added, "Through millions of simulations, we traced the origins of when and how ecDNA appears and makes tumors aggressive."
The research team explained that ecDNA contains multiple cancer genes at once, necessitating a personalized treatment strategy tailored to the characteristics of ecDNA specific to each patient. In particular, they expect that intervening in treatment during the short time frame from when EGFR ecDNA first appears to before more dangerous mutations arise could prevent cancer progression. Dr. Werner also remarked, "If we can detect early ecDNA mutations through methods like blood tests in the future, we may be able to start treatment before the cancer becomes more dangerous."
Professor Charlie Swanton from the Francis Crick Institute stated, "This research shows that ecDNA is not just a simple byproduct floating around but a powerful entity that promotes glioblastoma," and added, "Tracking the developmental process of ecDNA could pave the way for new advancements in both diagnosis and treatment."
The research team announced that they will further investigate how various treatment methods affect the quantity and types of ecDNA within glioblastoma.
Cancer Discovery (2025), DOI: www.doi.org/10.1158/2159-8290.CD-24-1555