[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-329415-105":3,"doc-detail-329415-en":81,"detail-sidebar-cat-0-en-105":99},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","mapping-extrachromosomal-dna-amplifications-during-cancer-progression","Mapping extrachromosomal DNA amplifications during cancer progression","","Mapping extrachromosomal DNA (ecDNA) amplifications during cancer progression across 8,060 newly diagnosed primary cancers, untreated metastases, and heavily pretreated tumors shows ecDNAs occur at significantly higher frequency in untreated metastatic and pretreated tumors than in newly diagnosed cancers. Longitudinally matched samples indicate ecDNAs are more often retained than chromosomal amplifications, while advanced cancers show greater localized hypermutation. Findings suggest ecDNAs provide competitive advantages supporting progression and metastasis.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/mapping-extrachromosomal-dna-amplifications-during-cancer-progression/329415/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/mapping-extrachromosomal-dna-amplifications-during-cancer-progression/329415.png","ImageObject",300,407,{"name":42,"@type":43},"Eden","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How were ecDNA amplifications mapped across the cancer cohorts?","Question",{"text":63,"@type":64},"The study detected and classified focal ecDNA amplifications across 8,060 newly diagnosed primary cancers, untreated metastases, and heavily pretreated tumors.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Do ecDNA frequencies differ between newly diagnosed cancers and advanced disease?",{"text":68,"@type":64},"Yes. ecDNAs were found at significantly higher frequency in untreated metastatic and pretreated tumors than in newly diagnosed cancers.",{"name":70,"@type":61,"acceptedAnswer":71},"What relationship did the study observe between ecDNA retention and chromosomal amplifications?",{"text":72,"@type":64},"In longitudinally matched samples, ecDNAs were more likely to be retained compared to chromosomal amplifications, and advanced cancers’ ecDNAs showed more localized hypermutation events.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},329415,1789996364,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98,"preview_page_count":4},1374391974468,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0",8,"nature genetics  \nArticle [https://doi.org/10.1038/s41588-024-01949-7](https://doi.org/10.1038/s41588-024-01949-7)  \nMapping extrachromosomal DNA amplifications during cancer progression  \nReceived: 13 December 2023  \nAccepted: 13 September 2024  \n\n| Published online: 14 October 2024 |\n| --- |\n|  Check for updates |\n\nHoon Kim  1,2,3,15,16, Soyeon Kim  1,4,15, Taylor Wade5, EunchaeYeo2, Anuja Lipsa  6, Anna Golebiewska  6, Kevin C. Johnson  4, SepilAn  1, Junyong Ko7, Yoonjoo Nam1, Hwa Yeon Lee8, Seunghyun Kang  1, Heesuk Chung1, Simone P. Niclou6,9, Hyo-Eun Moon10, Sun Ha Paek  10,11, Vineet Bafna12,13, Jens Luebeck  12 & RoelG. W. Verhaak  4,14,16  \nTo understand the role of extrachromosomal DNA (ecDNA) amplificationsin cancer progression, we detected and classified focal amplificationsin 8,060 newly diagnosed primary cancers, untreated metastases and heavily pretreated tumors. TheecDNAs were detected at significantly higher frequency in untreated metastatic and pretreated tumors compared to newly diagnosed cancers. Tumors from chemotherapy-pretreated patients showed significantly higher ecDNA frequency compared to untreated cancers. In particular, tubulin inhibition associated with ecDNA increases, suggesting a role forecDNAin treatment response. In longitudinally matched tumor samples, ecDNAs were more likely tobe retained compared to chromosomal amplifications. EcDNAs shared between time points, andecDNAsin advanced cancers were more likely to harbor localized hypermutation events compared to private ecDNAsandecDNAsin newly diagnosed tumors. Relatively high variant allele fractions of ecDNA localized hypermutations implicated early ecDNA mutagenesis. Our findings nominate ecDNAsto provide tumors with competitive advantages during cancer progression and metastasis.  \nDisease progression, including metastasis, is a leading cause of death from cancer as tumors acquire resistance and become increasingly less responsive to therapies1,2. Characterizing the genomic features of primary untreated and metastatic treated tumors is critical to improving our understanding of the processing driving cancer progression3,4. Cancer is driven by genomic alterations, including focal DNA amplifications, in which DNA segments containing oncogenes or oncogenic regulatory elements are multiplied, resulting in oncogene transcription and activation5. Amplifications may occur through mechanisms tethered to chromosomes, forming homogeneously staining regions (HSRs), or by excising and circularizing DNA segments to form extrachromosomal DNA (ecDNA) elements6,7. HSRsandecDNAs both create gene amplification, but their functional consequences may vary8,9. EcDNAs replicate with the linear genome but lack centromeres, resulting in uneven segregation and enabling  \nrapid accumulation of ecDNAs in tumor cell nuclei9,10. If the ecDNA endows the tumor cell with a competitive advantage, cells containingecDNAs undergo selection, creating a dominant tumor cell clone driven by an ecDNA-activated oncogene11. TheecDNAs are detected inmost human cancer types atthe time of diagnosis and are enriched in poor prognosis tumor types such as glioblastoma, sarcoma and esophageal carcinoma8. However, the role ofecDNAs in advanced cancers remains unclear.  \nThe genes carried on or activated by ecDNAs include ERBB2, EGFR and CDK4, which are targets of commonly used inhibitors for the treatment of patients with cancer. In addition, oncogenes that are considered undruggable are detected on ecDNAs, such as MYC, TERT and MCL1. Infact, all genes known tobe focally amplified incancer are detected on ecDNAs in some tumors8,12,13. The discovery of ecDNA clusters that appear to function as hubs where transcriptional  \nA full list of affiliations appears at the end of the paper. [e-mail:](e-mail: wisekh@skku.edu)[ wisekh@skku.edu](e-mail: wisekh@skku.edu); [roel.verhaak@yale.edu](roel.verhaak@yale.edu)  \nNature Genetics | Volume 56 | November 2024 | 2447–2454 2447  \na  \nSingle time poin","cbCaidXtjZBV9uaT","https://ap.wps.com/l/cbCaidXtjZBV9uaT","pdf",23042053,28,"English","# Sample classification\n## ecDNA detection across cohorts\n## Longitudinal retention and hypermutation events","[{\"question\":\"How were ecDNA amplifications mapped across the cancer cohorts?\",\"answer\":\"The study detected and classified focal ecDNA amplifications across 8,060 newly diagnosed primary cancers, untreated metastases, and heavily pretreated tumors.\"},{\"question\":\"Do ecDNA frequencies differ between newly diagnosed cancers and advanced disease?\",\"answer\":\"Yes. ecDNAs were found at significantly higher frequency in untreated metastatic and pretreated tumors than in newly diagnosed cancers.\"},{\"question\":\"What relationship did the study observe between ecDNA retention and chromosomal amplifications?\",\"answer\":\"In longitudinally matched samples, ecDNAs were more likely to be retained compared to chromosomal amplifications, and advanced cancers’ ecDNAs showed more localized hypermutation events.\"}]","Mapping extrachromosomal DNA amplifications during cancer progression | PDF",1789984062,71,{"code":4,"msg":82,"data":100},[101,105,109,113,118,123,128,131,136,139,142],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},5,"Comic",60,"comic",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},6,"Technology",50,"technology",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":126,"slug":127},7,"Healthcare",40,"healthcare",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":129,"slug":130},30,"research-report",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":134,"slug":135},9,"Religion & Spirituality",20,"religion-spirituality",{"id":134,"doc_module":4,"doc_module_name":25,"category_name":137,"show_sort_weight":134,"slug":138},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":140,"show_sort_weight":55,"slug":141},"Lifestyle","lifestyle",{"id":143,"doc_module":4,"doc_module_name":25,"category_name":144,"show_sort_weight":114,"slug":145},19,"General","general"]