[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-328344-105":59,"doc-detail-328344-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","clonal-expansion-in-normal-tissues","Clonal expansion in normal tissues","","Cancer develops from a single ancestral cell that gains a driver mutation, enabling growth or survival, and is followed by additional driver mutations in descendant lineages. Somatic mutations increasingly accumulate in normal tissues with aging and environmental exposures such as alcohol, smoking, and UV, raising mutation rates. Driver-bearing clones can then expand over time, contributing to tissue remodeling and revealing early, decades-long cancer development through lineage analysis. Clonal hematopoiesis also influences diverse diseases, motivating identification and functional study of mutated clones to clarify unknown pathologies.",{"@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/clonal-expansion-in-normal-tissues/328344/",{"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/clonal-expansion-in-normal-tissues/328344.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does cancer originate according to the review?","Question",{"text":112,"@type":113},"Cancer is described as a clonal disorder beginning with a single ancestral cell that acquires a driver mutation, followed by the stepwise acquisition of additional driver mutations in descendant cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role do somatic mutations play in normal tissues?",{"text":117,"@type":113},"Somatic mutations accumulate in normal tissues with aging and environmental exposures, increasing the mutation rate and enabling expansion of clones that carry driver mutations.",{"name":119,"@type":110,"acceptedAnswer":120},"What does lineage analysis reveal about the timing of cancer development?",{"text":121,"@type":113},"Lineage analysis of specific cancers shows that driver mutations are acquired early in life, and cancer development takes decades, uncovering an early process previously unknown.","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},328344,1790177818,{"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":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","Received: 7 February 2024 | Revised: 24 March 2024 | Accepted: 1 April 2024  \nDOI: 10. 1111/cas.16183  \nR E V I E W A RT I C L E  \nClonal expansion in normal tissues  \nHirona Maeda1,2 | Nobuyuki Kakiuchi1,3,4   \n1Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 2Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan 3The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan 4Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan  \nCorrespondence  \nNobuyuki Kakiuchi, Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606- 8501, Japan.  \nEmail: [kakiuchi@kuhp.kyoto-u.ac.jp](kakiuchi@kuhp.kyoto-u.ac.jp)  \nFunding information  \nPrincess Takamatsu Cancer Research Fund; Japan Science and Technology Agency, Grant/Award Number:  \nJPMJFR215V and JPMJMS2022; Japan Society for the Promotion of Science, Grant/Award Number: JP20H03513 and JP22K19457; Inoue Foundation for Science; Japan Agency for Medical Research and Development, Grant/Award Number: JP23ck0106798; Takeda Science Foundation  \nAbstract  \nCancer originates from a single ancestral cell that acquires a driver mutation, which confers a growth or survival advantage, followed by the acquisition of additional driver mutations by descendant cells. Recently, it has become evident that somatic cell mutations accumulate in normal tissues with aging and exposure to environmental factors, such as alcohol, smoking, and UV rays, increases the mutation rate. Clones harboring driver mutations expand with age, leading to tissue remodeling. Lineage analysis of myeloproliferative neoplasms and der(1;16)-positive breast cancer revealed that driver mutations were acquired early in our lives and that the development of cancer takes decades, unveiling the previously unknown early process of cancer development. Evidence that clonal hematopoiesis affects various diseases, including nonneoplastic diseases, highlights the potential role of the identification and functional analysis of mutated clones in unraveling unknown pathologies. In this review, we summarize the recent updates on clonal expansion in normal tissues and the natural history of cancer revealed through lineage analysis of noncancerous and cancerous tissues.  \nK E Y WO R D S  \naging, carcinogenesis, clonal evolution, mutation rate, phylogenetic analysis  \n1 | INTRODUCTION  \nCancer is a clonal disorder that arises from a single ancestral cell and its descendant cells undergoing positive selection within normal tissues, eventually deviating from homeostasis and exhibiting aberrant proliferation. The hypothesis that cancer originates from a single progenitor cell was proposed in the early 20th century,1 and the evolution of progenitor cells into cancer has been interpreted in the context of Darwinian evolution. 2,3 Within a genetically diverse population of cells, individual cells exhibit diverse phenotypes, and  \ncells that are advantageous for survival and proliferation are selectively expanded. This selection is influenced by factors, such as the microenvironment, anatomical structures, and therapeutic interventions, which shape the selective pressures. The detailed natural history of clonal evolution during the carcinogenic process has become evident only in recent years.  \nThe advent of next-generation sequencing has led to rapid progress in deciphering cancer genomes across various organs. Large-scale cancer genome projects, such as The Cancer Genome Atlas and the International Cancer Genome Consortium, have  \nAbbreviations: CH, clonal hematopoiesis; CNA, copy number alteration; HR, hazard ratio; SNV, single nucleotide variant.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work i","cbCaisLg84aEoyHt","https://ap.wps.com/l/cbCaisLg84aEoyHt","pdf",1832806,"English","# Abstract\n# Introduction\n# Somatic mutations in normal tissues","[{\"question\":\"How does cancer originate according to the review?\",\"answer\":\"Cancer is described as a clonal disorder beginning with a single ancestral cell that acquires a driver mutation, followed by the stepwise acquisition of additional driver mutations in descendant cells.\"},{\"question\":\"What role do somatic mutations play in normal tissues?\",\"answer\":\"Somatic mutations accumulate in normal tissues with aging and environmental exposures, increasing the mutation rate and enabling expansion of clones that carry driver mutations.\"},{\"question\":\"What does lineage analysis reveal about the timing of cancer development?\",\"answer\":\"Lineage analysis of specific cancers shows that driver mutations are acquired early in life, and cancer development takes decades, uncovering an early process previously unknown.\"}]","Clonal expansion in normal tissues | PDF",1789979394]