[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-328359-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-328359-en":130},{"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","evolutionary-history-of-adenomas-to-colorectal-cancer-in-fap-families-original-research","Evolutionary history of adenomas to colorectal cancer in FAP families - Original Research","","Familial adenomatous polyposis (FAP) progresses, without treatment, from multiple adenomatous stages to colorectal cancer (CRC). This study reconstructs the evolutionary history from precancerous adenomas to carcinoma using exome sequencing across gastrointestinal tissues and matched blood samples from Chinese FAP families. Germline APC variants were identified, adenomas showed lower mutational burdens, and progressive genomic-scarring HRD increases tracked the adenoma-to-carcinoma transition. TP53 was highlighted as a key driver, supporting a classical cancerization model.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/evolutionary-history-of-adenomas-to-colorectal-cancer-in-fap-families-original-research/328359/",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/evolutionary-history-of-adenomas-to-colorectal-cancer-in-fap-families-original-research/328359.png","ImageObject",300,407,{"name":42,"@type":43},"Noah","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main objective of this study on FAP-associated CRC?","Question",{"text":63,"@type":64},"To reconstruct the evolutionary history from precancerous adenoma to carcinoma in familial adenomatous polyposis (FAP) families and clarify the temporal sequence of events leading to CRC.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were the samples and sequencing performed?",{"text":68,"@type":64},"Tissues were collected from gastrointestinal endoscopy or surgical resection, and exome sequencing was performed on multiple adenoma and carcinoma regions; blood samples were obtained from patients in seven Chinese FAP families.",{"name":70,"@type":61,"acceptedAnswer":71},"Which gene was identified as the primary driver during the adenoma-to-carcinoma transition?",{"text":72,"@type":64},"TP53 emerged as the primary driver gene, with driver mutations appearing simultaneously rather than sequentially acquired from adenomas to carcinomas.","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},328359,1790137520,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","TYPE Original Research PUBLISHED 03 July 2024  \nDOI 10.3389/fgene.2024.1391851  \nOPEN ACCESS  \nEDITED BY  \nThierry Mp Gauthier,  \nNational Institutes of Health (NIH), United States  \nREVIEWED BY  \nDahmane Oukrif,  \nUniversity College London, United Kingdom Liliana C. Patiño Molano,  \nNational Institute of Dental and Craniofacial Research (NIH), United States  \n*CORRESPONDENCE  \nXuqian Fang,  \n [251720307@qq.com](251720307@qq.com)  \n†These authors have contributed equally to this work  \nRECEIVED 26 February 2024  \nACCEPTED 04 June 2024  \nPUBLISHED 03 July 2024  \nCITATION  \nYang C, Xiang E, Chen P and Fang X (2024), Evolutionary history of adenomas to colorectal cancer in FAP families.  \nFront. Genet. 15:1391851 .  \ndoi: 10.3389/fgene.2024.1391851  \nCOPYRIGHT  \n© 2024 Yang, Xiang, Chen and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nEvolutionary history of adenomasto colorectal cancer in  \nFAP families  \nCuiping Yang 1†, Enfei Xiang 2†, Ping Chen 1 and Xuqian Fang 3*  \n1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China  \nObjective: Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by multiple polyps at various evolutionary stages, which, if left untreated, inevitably progress to colorectal cancer (CRC) . In this study, we present a comprehensive analysis of the evolutionary history of FAP-CRC from precancerous adenoma to carcinoma.  \nDesign: Tissues were collected from gastrointestinal endoscopy or surgical resection. Exome sequencing was performed on multiple regions ofadenocarcinoma (n = 8), villous adenoma (n = 10), tubular adenoma (n = 9) and blood samples were obtained from 9 patients belonging to 7 Chinese FAP families. Phylogenetic trees were reconstructed, and evolutionary analysis was conducted to reveal the temporal sequence of events leading to CRC.  \nResults: Inherited germline mutation sites in APC gene were identified in FAP01 (p. S1281*, COSM19212), FAP03 (p. S384Tfs*19), FAP04 (p. E1538*, COSM6041693), FAP05 (p.Q1062*, COSM3696862), and FAP07-FAP09 (p.V677Sfs*3) . Notably, p.V677Sfs*3 mutation was recognized as a novel germline mutation in APC, supported by evidence of genotype-phenotype correlation in pedigree analysis. Adenomas exhibited lower mutational rates than FAP-CRC and displayed recurrent alterations in well-known chromosomal instability (CIN) genes (APC, RAS, SMAD4 and TP53) and DNA damage repair genes (SUZ12, KMT2C, BCLAF1, RUNX1, and ARID1B), suggesting the presence of genomic instability. Furthermore, a progressive increase in the HRD score (a measure of “genomic scars”) was observed from tubular adenomasto villous adenomas and ultimately to carcinomas. TP53 emerged as the primary driver gene for adenoma-carcinoma transition, with driver mutations consistently appearing simultaneously rather than sequentially acquired from adenomas to carcinomas. Clonal evolution demonstrated that liver metastases can originate from the same cancer-primed cell present in a primary cancerous lesion.  \nConclusion: We identified a novel pathogenic variant in APC, namely, p.V677Sfs*3 . The process of carcinogenesis in FAP-CRC supports the classical cancerization model, where an initial APC mutation leads to the activation of the WNT signaling pathway and CIN. Subsequently, additional mutations occu","cbCaiuRe0mRO6Mb6","https://ap.wps.com/l/cbCaiuRe0mRO6Mb6","pdf",2198571,11,"English","# Objective\n# Design\n# Results\n# Conclusion\n# Introduction","[{\"question\":\"What is the main objective of this study on FAP-associated CRC?\",\"answer\":\"To reconstruct the evolutionary history from precancerous adenoma to carcinoma in familial adenomatous polyposis (FAP) families and clarify the temporal sequence of events leading to CRC.\"},{\"question\":\"How were the samples and sequencing performed?\",\"answer\":\"Tissues were collected from gastrointestinal endoscopy or surgical resection, and exome sequencing was performed on multiple adenoma and carcinoma regions; blood samples were obtained from patients in seven Chinese FAP families.\"},{\"question\":\"Which gene was identified as the primary driver during the adenoma-to-carcinoma transition?\",\"answer\":\"TP53 emerged as the primary driver gene, with driver mutations appearing simultaneously rather than sequentially acquired from adenomas to carcinomas.\"}]","Evolutionary history of adenomas to colorectal cancer in FAP families - Original Research | PDF",1789979454,28]