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| Item Type: | Preprint |
|---|---|
| Title: | Extrachromosomal DNA associates with poor survival across a broad spectrum of childhood solid tumors |
| Creators Name: | Chapman, Owen S., Sridhar, Sunita, Chow, Eugene Yui-Ching, Kenkre, Rishaan, Kirkland, Jonathan, Dutta, Aditi, Wang, Shanqing, Zhang, Wenshu, Brown, Miguel, Luebeck, Jens S, Lo, Yan Yuen, Rodriguez-Fos, Elias, Henssen, Anton G., Okonechnikov, Konstantin, Ghasemi, David R., Pajtler, Kristian W., Kawauchi, Daisuke, Bafna, Vineet, Paul, Megan, Yip, Kevin, Mesirov, Jill P. and Chavez, Lukas |
| Abstract: | Circular extrachromosomal DNA (ecDNA) is a common form of oncogene amplification in aggressive cancers. The frequency and diversity of ecDNA has been catalogued in adult and some childhood cancers; however, its role in most pediatric cancers is not well-understood. To address this gap, we accessed large pediatric cancer genomics data repositories and identified ecDNA from whole genome sequencing data using cloud computing. This retrospective cohort comprises 3,631 solid tumor biopsies from 2,968 patients covering all major childhood solid tumor types. Aggressive tumor types had particularly high incidences of ecDNA. Pediatric patients whose tumors harbored extrachromosomal DNA had significantly poorer five-year overall survival than children whose tumors contained only chromosomal amplifications. We catalogue known and potentially novel oncogenes recurrently amplified on ecDNA and show that ecDNA often evolves during disease progression. These results highlight patient populations that could potentially benefit from future ecDNA-directed therapies. To facilitate discovery, we developed an interactive catalogue of ecDNA in childhood cancer at https://ccdi-ecdna.org/. |
| Source: | medRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.07.22.24308163v2 |
| Date: | 7 August 2025 |
| Official Publication: | https://doi.org/10.1101/2025.07.22.24308163 |
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