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This study tested whether genomic alterations in histologically non-dysplastic resection margins relate to subsequent neoplastic progression after UC-associated dysplasia removal. A retrospective cohort of 51 patients underwent low-coverage whole genome sequencing of dysplastic lesions and adjacent margins, linking copy number alteration burden and phylogeny to progression.",{"@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":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/genomic-alterations-in-histologically-clear-low-grade-dysplasia-resection-margins-forecast-advanced-neoplasia-in-ulcerative-colitis/461461/",{"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/genomic-alterations-in-histologically-clear-low-grade-dysplasia-resection-margins-forecast-advanced-neoplasia-in-ulcerative-colitis/461461.png","ImageObject",300,407,{"name":92,"@type":93},"Fahsai","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-10","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why do some ulcerative colitis patients develop advanced neoplasia after histologically complete endoscopic resection?","Question",{"text":112,"@type":113},"Some patients progress to advanced neoplasia despite clear histological margins, likely because the surrounding tissue may contain a cancerised genomic field not captured by standard histopathology.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What was the study objective in this research?",{"text":117,"@type":113},"To determine whether genomic alterations within histologically non-dysplastic resection margins are associated with subsequent neoplastic progression after endoscopic resection of UC-associated dysplasia.",{"name":119,"@type":110,"acceptedAnswer":120},"Which genomic finding was linked to local progression to advanced neoplasia?",{"text":121,"@type":113},"Higher somatic copy number alteration (CNA) burden in histologically non-dysplastic margins was independently associated with local progression, whereas histological clearance and en bloc excision were not.","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},461461,1790941596,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"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":145,"preview_page_count":4},549768702563,"https://ap-avatar.wpscdn.com/avatar/8000c4aa63b76e948b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786536092046926083","medRxiv preprint doi: [https://doi.org/10.64898/2026.09.10.26362759](https://doi.org/10.64898/2026.09.10.26362759); this version posted September 11, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-NC 4.0 International license .  \nGenomic alterations in histologically clear low grade dysplasia resection margins forecast advanced neoplasia in ulcerative colitis  \nJennifer Fisher*,1,2 Konstantin Bräutigam*1,3, Heather E Grant1, Maximilian Mossner1, Chirine Sakr1, Ibrahim Al Bakir4, Brian Saunders2, Noriko Suzuki2, Ana Wilson2, Ann-Marie Baker1\\#, Ailsa Hart 2\\#, Trevor A Graham1\\#  \n1Centre for Evolution and Cancer, Institute of Cancer Research, London, United Kingdom  \n2 Inflammatory Bowel Disease Unit, St Mark's Hospital, Harrow, United Kingdom 3 Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland 4Chelsea and Westminster Hospital, London, United Kingdom  \n*Joint 1st authors  \n\\#co-senior authors  \nKey words: sequencing; copy number alteration; ulcerative colitis; aneuploidy; inflammatory bowel disease; progression; biomarker  \nNOTE: This preprint reports new research that has not been certifid by peer review and should not be used to guide clinical practice.  \nmedRxiv preprint doi: [https://doi.org/10.64898/2026.09.10.26362759](https://doi.org/10.64898/2026.09.10.26362759); this version posted September 11, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-NC 4.0 International license .  \nAbstract  \nBackground  \nEndoscopic resection is used for the management of dysplasia in ulcerative colitis (UC), but a subset of patients develop subsequent advanced neoplasia (AN), i.e., high-grade dysplasia and/or colorectal cancer, despite apparently complete resection with histologically clear margins. Current risk stratification relies predominantly on histopathological and procedural features, which does not capture underlying genomic field cancerization of morphologically normal mucosa.  \nObjective  \nTo determine whether genomic alterations within histologically non-dysplastic resection margins are associated with subsequent neoplastic progression following endoscopic resection of UC-associated dysplasia.  \nDesign  \nWe analysed a retrospective cohort of 51 UC patients, who underwent endoscopic resection of dysplastic lesions at a tertiary referral centre, with a median follow-up of 1947 days. 11 of these had local progression. We performed low-coverage whole genome sequencing (lcWGS) of 56 dysplastic lesions and 91 adjacent histologically non-dysplastic margins. Somatic copy number alteration (CNA) burden and phylogenetic analysis were correlated with progression to AN .  \nResults  \nHistologically non-dysplastic margins from lesions that subsequently progressed to AN demonstrated significantly higher CNA burden compared with non-progressors. In multivariate analysis high margin CNA burden was independently associated with local progression, whereas histologically clear resection margins and en bloc excisions were not.  \nConclusion  \nHistological clearance does not necessarily indicate clearance of the cancerised field in UCassociated dysplasia. Genomic detection of field cancerisation within histologically nondysplastic resection margins identifies patients at increased risk of subsequent neoplasia and provides a potential biomarker for biologically informed post-resection surveillance.  \nmedRxiv preprint doi: [https://doi.org/10.64898/2026.09.10.26362759](https://doi.org/10.64898/2026.09.10.26362759); this version posted September 11, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv","cbCaikjDnK5CvXWn","https://ap.wps.com/l/cbCaikjDnK5CvXWn","pdf",12331028,23,"English","# Abstract\n## Background\n## Objective\n## Design\n## Results\n## Conclusion\n# What is already known on this topic\n# What this study adds\n# How this study might affect research, practice or policy\n# Introduction","[{\"question\":\"Why do some ulcerative colitis patients develop advanced neoplasia after histologically complete endoscopic resection?\",\"answer\":\"Some patients progress to advanced neoplasia despite clear histological margins, likely because the surrounding tissue may contain a cancerised genomic field not captured by standard histopathology.\"},{\"question\":\"What was the study objective in this research?\",\"answer\":\"To determine whether genomic alterations within histologically non-dysplastic resection margins are associated with subsequent neoplastic progression after endoscopic resection of UC-associated dysplasia.\"},{\"question\":\"Which genomic finding was linked to local progression to advanced neoplasia?\",\"answer\":\"Higher somatic copy number alteration (CNA) burden in histologically non-dysplastic margins was independently associated with local progression, whereas histological clearance and en bloc excision were not.\"}]","Genomic alterations in histologically clear low grade dysplasia resection margins forecast advanced neoplasia in ulcerative colitis | PDF",1790761668,58]