[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331386-105":59,"doc-detail-331386-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","apc-mutations-dysregulate-alternative-polyadenylation-in-cancer","APC mutations dysregulate alternative polyadenylation in cancer","","Alternative polyadenylation (APA) shapes mRNA processing across most human genes and is repeatedly disrupted in cancers, yet its underlying mechanisms remain unclear. This study performs an unbiased analysis of poly(A) site–selection regulators across The Cancer Genome Atlas, pinpointing colorectal adenocarcinoma as an outlier linked to loss-of-function APC mutations and long 3′ UTR expression. APC eCLIP data show preferential binding near proximal poly(A) sites, while APC knockout in colon organoids and reduced APC expression in other tumors reproduce APA dysregulation.",{"@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/apc-mutations-dysregulate-alternative-polyadenylation-in-cancer/331386/",{"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/apc-mutations-dysregulate-alternative-polyadenylation-in-cancer/331386.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the paper investigate about alternative polyadenylation (APA)?","Question",{"text":112,"@type":113},"It examines how APA is dysregulated in cancers and specifically seeks mechanistic sources for this widespread disruption.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is colorectal adenocarcinoma identified as different from other cancer subtypes?",{"text":117,"@type":113},"An unbiased regulator analysis across TCGA shows colorectal adenocarcinoma is an outlier, associated with frequent loss-of-function APC mutations and long 3′ UTR expression.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does APC play according to the study results?",{"text":121,"@type":113},"APC promotes proximal poly(A) site use; loss of APC function or reduced APC expression is linked to APA dysregulation, supported by organoid knockout effects and APC eCLIP binding patterns.","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},331386,1790232840,{"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":44,"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,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Gabel et al. Genome Biology (2024) 25:255 [https://doi.org/10.1186/s13059-024-03406-4](https://doi.org/10.1186/s13059-024-03406-4)  \nGenome Biology  \nRESEARCH Open Access  \nAPC mutations dysregulate alternative polyadenylation in cancer  \nAustin M. Gabel 1,2,3,4, Andrea E. Belleville 1,2,3,5, James D. Thomas 1,2, Jose Mario Bello Pineda 1,2,3,4 and Robert K. Bradley 1,2,3*  \n*Correspondence: [rbradley@fredhutch.org](rbradley@fredhutch.org)  \n1 Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA  \n2 Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA  \n3 Department of Genome Sciences, University of Washington, Seattle, WA, USA  \n4 Medical Scientist Training Program, University of Washington, Seattle, WA, USA  \n5 Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA  \nAbstract  \nBackground: Alternative polyadenylation (APA) affects most human genes  \nand is recurrently dysregulated in all studied cancers. However, the mechanistic origins of this dysregulation are incompletely understood.  \nResults: We describe an unbiased analysis of molecular regulators of poly(A) siteselection across The Cancer Genome Atlas and identify that colorectal adenocarcinoma is an outlier relative to all other cancer subtypes. This distinction arises from the frequent presence of loss-of-function APC mutations in colorectal adenocarcinoma, which are strongly associated with long 3′ UTR expression relative to tumors lacking APC mutations. APC knockout similarly dysregulates APA in human colon organoids. By mining previously published APC eCLIP data, we show that APC preferentially binds G-and C-rich motifs just upstream of proximal poly(A) sites. Lastly, we find that reduced APC expression is associated with APA dysregulation in tumor types lacking recurrent APC mutations.  \nConclusions: As APC has been previously identified as an RNA-binding protein  \nthat preferentially binds 3′ UTRs during mouse neurogenesis, our results suggest that APC promotes proximal poly(A) site use and that APC loss and altered expression contribute to pervasive APA dysregulation in cancers.  \nBackground  \nAlternative cleavage and polyadenylation (APA) occurs in a majority of human genes and is known to vary across cell types and biological contexts, including cancer [1–6]. Mechanistic study of distinct APA events demonstrates that changes in poly(A) siteselection can alter mRNA stability, translation kinetics, and localization [7–9]. APA is globally dysregulated in all studied human cancers [10, 11], and alterations in APA correlate with clinically relevant cancer phenotypes such as patient prognosis, immune infiltration, and others [10, 12–14].  \nAlthough canonical protein regulators of APA and 3′ end processing of mRNAs have been well studied and demonstrated to contribute to cancer-associated dysregulation  \n© The Author(s) 2024, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise ina credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.)  \nGabel et al. Genome Biology (2024) 25:255 Page 2 of 16  \nof APA, the mechanist","cbCaikByhSmoCAK2","https://ap.wps.com/l/cbCaikByhSmoCAK2","pdf",25451884,16,"English","# Abstract\n## Background\n## Results\n## Conclusions\n# Background\n## Mechanistic context of APA in cancer\n# Results\n## Canonical APA regulators across cancer subtypes","[{\"question\":\"What does the paper investigate about alternative polyadenylation (APA)?\",\"answer\":\"It examines how APA is dysregulated in cancers and specifically seeks mechanistic sources for this widespread disruption.\"},{\"question\":\"How is colorectal adenocarcinoma identified as different from other cancer subtypes?\",\"answer\":\"An unbiased regulator analysis across TCGA shows colorectal adenocarcinoma is an outlier, associated with frequent loss-of-function APC mutations and long 3′ UTR expression.\"},{\"question\":\"What role does APC play according to the study results?\",\"answer\":\"APC promotes proximal poly(A) site use; loss of APC function or reduced APC expression is linked to APA dysregulation, supported by organoid knockout effects and APC eCLIP binding patterns.\"}]","APC mutations dysregulate alternative polyadenylation in cancer | PDF",1789993091]