Megabase-sized extrachromosomal circular DNA with intact oncogenes (ecDNA) plays crucial roles in cancer. However, the impact of smaller (100 bp-1 Mb), more ubiquitous extrachromosomal circular DNA (eccDNA) on tumor pathology is unclear. We analyze eccDNA from 122 renal tumors and adjacent tissues, finding increased eccDNA in late-stage cancers, correlating with heightened patient mortality and copy-number amplification. Large eccDNAs are rare, and smaller eccDNAs predominate. The microRNA (miRNA) genes MIR107, MIR196a, MIR495, and MIR519 are recurrently found on eccDNA, almost exclusively in tumors, and patients with any one of these exhibited shorter progression-free survival. Synthetic eccDNAs with these MIR genes increase cancer cell proliferation in 786-O cells, suggesting oncogenic potential. Additionally, we found eccDNA carrying full protein-coding genes that are overexpressed in transcriptional analyses. Our findings suggest that small eccDNAs with miRNA genes are functional and contribute to the tumorigenesis of renal cell carcinoma.
Keywords: CP: cancer; double minutes; ecDNA; eccDNA; extrachromosomal circular DNA; renal cell carcinoma.
Copyright © 2025. Published by Elsevier Inc.