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This study quantifies de novo L1 insertions in clinical high-grade serous ovarian cancer specimens, revealing strong patient-to-patient heterogeneity in L1 burden. Tumors with high L1 burden show enhanced proliferation, while low/no L1 insertions enrich immune response and cell death pathways. L1 activity is dynamic in vivo and supports tumor genome plasticity and intrapatient heterogeneity.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dynamic-and-ongoing-de-novo-l1-retrotransposition-contributes-to-genome-plasticity-and-intrapatient-heterogeneity-in-ovarian-cancer-research-findings/348990/",{"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/dynamic-and-ongoing-de-novo-l1-retrotransposition-contributes-to-genome-plasticity-and-intrapatient-heterogeneity-in-ovarian-cancer-research-findings/348990.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do L1 retrotransposons play in ovarian cancer progression?","Question",{"text":112,"@type":113},"L1 retrotransposons are highly expressed in epithelial cancers, including high-grade serous ovarian cancer, and can create de novo genome insertions. These insertions are linked to genomic instability, cancer evolution, and intrapatient heterogeneity, supporting late-stage tumor genome plasticity.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the study characterize de novo L1 insertions in HGSC patients?",{"text":117,"@type":113},"The study quantifies de novo L1 insertions in clinical HGSC specimens. It identifies high heterogeneity across patients in total L1 insertion events (L1 burden) and examines how insertions differ among tumor sites within the same patient.",{"name":119,"@type":110,"acceptedAnswer":120},"How do tumor phenotypes differ between high and low L1 burden tumors?",{"text":121,"@type":113},"HGSC tumors with high L1 burden are highly proliferative. Tumors with low or no L1 insertions show enrichment of immune response and cell death pathways.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},348990,1790174736,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Dynamic and Ongoing De Novo L1 Retrotransposition Contributes to Genome Plasticity and Intrapatient Heterogeneity in Ovarian Cancer  \nBarun Pradhan1,2, Jaana Oikkonen1, Kaiyang Zhang3, Juan Manuel Botto4, Minna R. Eriksson1, Srividhya Sundaresan1, Fatih Genç1, Thomas R. Pisanic II5,6, Mat´ıas Marn Falco1, Yilin Li1,  \nSanna Pikkusaari1, Kari Lavikka1, Giulia Micoli1, Giovanni Marchi1, Taru A. Muranen1, Kaisa Huhtinen7, Anna Vhrautio1, Richard Badge8, Kathleen H. Burns9,10, Sakari Hietanen11, Johanna Hynninen11, Geoffrey J. Faulkner2,4, Sampsa Hautaniemi1, and Liisa Kauppi1  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n|  | Long interspersed element-1 (L1) retrotransposons are the only protein-coding active transposable elements in the human genome. Although typically silenced in normal cells, they are highly expressed in many human epithelial cancers, including high-grade serous ovarian cancer (HGSC), and can integrate into the genome through retrotransposition. De novo L1 insertions are known to contribute to genomic instability and cancer evolution in epithelial malignancies, including HGSC, suggesting that they might also play a role in intrapatient tumor heterogeneity. In this study, we quantified de novo L1 insertions in clinical HGSC specimens and uncovered high heterogeneity in total L1 insertion events (L1 burden) between patients. HGSC tumors with high L1 burden were highly proliferative, whereas tumors with low or no L1 insertions showed enrichment of immune response and cell death pathways. Although the overall L1 burden was similar\u003Cbr>􀀶 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | across different tumor sites within the same patient, the specific L1 insertions (L1 profiles) diverged significantly more than their single-nucleotide variants profiles. Taken together, these findings demonstrate that L1 activity and retrotransposition are highly dynamic in vivo and can contribute substantially to tumor genome plasticity, especially at late stages of cancer progression. The patient-specific propensity of acquiring L1 insertions (L1 burden) could be driven by molecular properties of the progenitor tumor. Retrotransposition-associated DNA damage and/or replication stress could be a potential molecular vulnerability for precision cancer medicine approaches.\u003Cbr>Significance: L1 retrotransposition is a dynamic process that continues at late stages of high-grade serous ovarian cancer and can substantially contribute to intrapatient tumor heterogeneity. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n\nIntroduction  \nLong INterspersed Element-1 (LINE-1 or L1) retrotransposons are the only active, protein-coding family of transposable elements in the human genome. They move via an RNA intermediate by a copy-and-paste mechanism called retrotransposition, using two selfencoded proteins called L1-ORF1p and L1-ORF2p. As a consequence, a new copy (L1 repeat sequence) is inserted into a","cbCaijamtA3xqpTh","https://ap.wps.com/l/cbCaijamtA3xqpTh","pdf",12681665,16,"English","# Introduction\n## L1 retrotransposons and retrotransposition mechanism\n## L1 activity in epithelial cancers and driver vs passenger insertions\n## HGSC background and L1 dysregulation","[{\"question\":\"What role do L1 retrotransposons play in ovarian cancer progression?\",\"answer\":\"L1 retrotransposons are highly expressed in epithelial cancers, including high-grade serous ovarian cancer, and can create de novo genome insertions. These insertions are linked to genomic instability, cancer evolution, and intrapatient heterogeneity, supporting late-stage tumor genome plasticity.\"},{\"question\":\"How does the study characterize de novo L1 insertions in HGSC patients?\",\"answer\":\"The study quantifies de novo L1 insertions in clinical HGSC specimens. It identifies high heterogeneity across patients in total L1 insertion events (L1 burden) and examines how insertions differ among tumor sites within the same patient.\"},{\"question\":\"How do tumor phenotypes differ between high and low L1 burden tumors?\",\"answer\":\"HGSC tumors with high L1 burden are highly proliferative. Tumors with low or no L1 insertions show enrichment of immune response and cell death pathways.\"}]","Dynamic and Ongoing De Novo L1 Retrotransposition Contributes to Genome Plasticity and Intrapatient Heterogeneity in Ovarian Cancer - Research findings | PDF",1790081040]