A bibliometric analysis of extrachromosomal DNA in cancer over six decades

Extrachromosomal DNA (ecDNA) is a critical driver of oncogene amplification and has significantly advanced the understanding of tumor heterogeneity. Although the biological mechanisms and clinical significance of ecDNA have been extensively studied, few articles have systematically summarized the historical development of this field. This study conducted a comprehensive retrospective analysis to map the evolutionary trajectory and research hotspots of ecDNA research in cancer from 1965 to 2025. We retrieved 3,328 publications from the Web of Science Core Collection and Scopus. We analyzed the co-authorship coverage alongside co-citation and co-occurrence of regions, institutions, authors, and keywords using VOSviewer and CiteSpace. The United States and China acted as the predominant global contributors, accounting for 38.25% and 25.81% of publications, respectively. Keyword co-occurrence and burst detection analyses revealed the thematic evolution of the field. Early dominant terms such as "gene amplification" focused on copy number variation in the linear genome without in-depth structural exploration. Contemporary research has shifted to terms including "circular DNA", "chromatin topology", and "drug resistance". This evolution signifies a paradigm shift from linear genome investigations to epigenetic mechanisms and clinical applications. We also discussed development prospects and key challenges while proposing potential solutions to major obstacles. This study aims to provide novel perspectives for advancing ecDNA research and its clinical translation in precision oncology.