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Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified “heterocateny,” a distinct genomic structural variation featuring diverse, interrelated, repetitive patterns of concatemerized viral and host segments. Shared breakpoints enabled stepwise reconstruction from a common ancestor. Heterocateny drives instability of viral and viral–host concatemers, promoting capture, amplification, recombination, and chromosomal rearrangements, and it supports intratumoral heterogeneity and clonal evolution.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/intratumoral-heterogeneity-and-clonal-evolution-induced-by-hpv-integration/378760/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/intratumoral-heterogeneity-and-clonal-evolution-induced-by-hpv-integration/378760.png","ImageObject",300,407,{"name":92,"@type":93},"Olivia Brown","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What new genomic structural variation did the study identify in HPV-positive tumors?","Question",{"text":113,"@type":114},"The study identified “heterocateny,” characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did long-read sequencing contribute to understanding heterocateny evolution?",{"text":118,"@type":114},"Unique breakpoints shared across structural variants enabled stepwise reconstruction of heterocateny evolution from a common molecular ancestor using continuous long-read sequencing data.",{"name":120,"@type":111,"acceptedAnswer":121},"What role does HPV integration play in promoting tumor evolution according to the findings?",{"text":122,"@type":114},"HPV integration induces aberrant replication and recombination of an oncogenic DNA virus, making heterocateny drive intratumoral heterogeneity and clonal evolution.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},378760,1790762754,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","RESEARCH ARTICLE  \nIntratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration   \nKeiko Akagi1, David E. Symer2, Medhat Mahmoud3, Bo Jiang1, Sara Goodwin4, Darawalee Wangsa5, Zhengke Li1, Weihong Xiao1, Joe Dan Dunn1, Thomas Ried5, Kevin R. Coombes6, Fritz J. Sedlazeck3,7, and Maura L. Gillison1  \nABSTRACT  The human papillomavirus (HPV) genome is integrated into host DNA in most HPVpositive cancers, but the consequences for chromosomal integrity are unknown.  \nContinuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified a previously undescribed form of structural variation,“heterocateny,” characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer. Unique breakpoints shared across structural variants facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that virus and virus–host concatemers are unstable and, upon insertion into and excision from chromosomes, facilitate capture, amplification, and recombination of host DNA and chromosomal rearrangements. Evidence of heterocateny was detected in extrachromosomal and intrachromosomal DNA. These findings indicate that heterocateny is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intratumoral heterogeneity and clonal evolution.  \nSIGNIFICANCE: Long-read sequencing of HPV-positive cancers revealed “heterocateny,” a previously unreported form of genomic structural variation characterized by heterogeneous, interrelated, and repetitive genomic rearrangements within a tumor. Heterocateny is driven by unstable concatemerized HPV genomes, which facilitate capture, rearrangement, and amplification of host DNA, and promotes intratumoral heterogeneity and clonal evolution.  \nSee related video: [https://vimeo.com/845407469](https://vimeo.com/845407469)  \n[See related commentary by McBride and White](See related commentary by McBride and White), p. 814.  \nINTRODUCTION  \nHuman papillomavirus (HPV) causes more than 630,000 cancers worldwide each year, including anogenital and oropharyngeal squamous cell carcinomas ( 1∼). Early in infection,  \nthe viral genome is maintained as an 8-kilobase pair (kb) extrachromosomal circular DNA (ecDNA)—that is, an episome. In a majority of subsequent cancers, HPV DNA has integrated into the host genome, connecting viral and cellular DNAs at breakpoints (2–5) in intrachromosomal DNA (icDNA) and/ or ecDNA forms (6). HPV integration promotes tumorigenesis by increasing expression and stability of transcripts encoding  \n1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas. 4Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. 5National Cancer Institute, Bethesda, Maryland.  \n6Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio. 7Department of Computer Science, Rice University, Houston, Texas. Note: K. Akagi and D.E. Symer share first authorship of this article. Current address for D.E. Symer: 10x Genomics, Pleasanton, California; current address for Z. Li, Boundless Bio, La Jolla, California; and current address for K.R. Coombes, Department of Population Health Science, Medical College of Georgia, Augusta University, Augusta, Georgia. Corresponding Author: Maura L. Gillison, Department of Thoracic/ Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030. Phone: 713-792-6363; E-mail: [mgillison@mdanderson.org](mgillison@mdanderson.org)  \nCancer Discov 2023;13:910–27  \ndoi: 10. 1158/2159-8290 ","cbCaiixEy3NKrtan","https://ap.wps.com/l/cbCaiixEy3NKrtan","pdf",11680218,18,"English","# Abstract\n# Significance\n# Introduction\n## Background on HPV infection and integration\n## Rationale and study approach\n# Results","[{\"question\":\"What new genomic structural variation did the study identify in HPV-positive tumors?\",\"answer\":\"The study identified “heterocateny,” characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.\"},{\"question\":\"How did long-read sequencing contribute to understanding heterocateny evolution?\",\"answer\":\"Unique breakpoints shared across structural variants enabled stepwise reconstruction of heterocateny evolution from a common molecular ancestor using continuous long-read sequencing data.\"},{\"question\":\"What role does HPV integration play in promoting tumor evolution according to the findings?\",\"answer\":\"HPV integration induces aberrant replication and recombination of an oncogenic DNA virus, making heterocateny drive intratumoral heterogeneity and clonal evolution.\"}]","Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration | PDF",1790232257,45]