Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular eukaryotes.Their biogenesis and function are po...Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular eukaryotes.Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are available.Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research hotspot.Several mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification models.Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health.The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites.The present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction.We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic tumors.This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.展开更多
基金supported by the National Natural Science Foundation of China [Grant Nos.32170493,32170656]the National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital)[Grant No.BYSYSZKF2022005]the Clinical Medicine Plus X-Young Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities (PKU2023LCXQ036)。
文摘Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular eukaryotes.Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are available.Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research hotspot.Several mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification models.Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health.The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites.The present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction.We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic tumors.This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
