Key Findings
Researchers at Sanford Burnham Prebys Medical Discovery Institute and colleagues published a study in Genome Medicine on May 28, 2026, demonstrating that patient-derived xenograft (PDX) models closely recapitulate the presence and sequence of circular extra-chromosomal DNA (ecDNA) found in primary pediatric tumors.
- The study analyzed nearly 300 pediatric tumor samples across 31 cancer types and corresponding PDX models.
- ecDNAs were found in approximately one-third of tumor samples. These ecDNAs carried extra copies of oncogenes, consistent with patterns from larger pediatric tumor studies.
- For over 80% of the PDX models, ecDNA presence matched the primary tumor. EcDNA sequences were largely conserved between tumor and model.
- In cases where ecDNA was present in a minority of tumor cells, those cells preferentially expanded in the PDX model, suggesting a selective advantage conferred by ecDNA.
Background
Circular extra-chromosomal DNA elements (ecDNA) were first described in 1965. In 1978, ecDNA was linked to drug resistance in mouse cancer models.
More recent studies have linked ecDNA to aggressive tumor types and worse clinical outcomes.
PDX models are created by grafting human tumor cells into mice and are widely used for cancer research and drug testing, but their validity for studying ecDNA had been uncertain.
Methodology
The research team compared genome sequencing data from nearly 300 pediatric tumor samples with their corresponding PDX models. They also used single-cell sequencing on two brain tumor-PDX model pairs to assess ecDNA distribution at the cellular level.
Statements
Lukas Chavez, PhD, senior and corresponding author: "For more than 80% of the PDX models, the presence of ecDNA was consistent with their primary tumors. The ecDNA sequences were largely the same across these pairs as well."
Rishaan Kenkre, lead author: "The ecDNA-positive cells from the human tumor, despite comprising only a small minority of the tumor population, exclusively grew out into the PDX model. At least for this specific pair, this led us to infer that ecDNAs can provide a selective advantage as the PDX model develops."
Conclusions
The authors conclude that PDX models are valid tools for studying how ecDNAs contribute to cancer progression and treatment resistance. The team plans to use these models to investigate ecDNA evolution under treatment stress and identify potential therapeutic targets.
Funding and DOI
The study was supported by the NIH, NCI, NINDS, NSF, Clayes Foundation, St. Baldrick and Dragon Master Foundation.
DOI: 10.1186/s13073-026-01676-0