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It further highlights evidence connecting many DNAm changes to cell proliferation, motivating epigenetic mitotic-like clocks and an entropy-promoting cancer stem-cell state.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/on-epigenetic-stochasticity-entropy-and-cancer-risk/331896/",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/on-epigenetic-stochasticity-entropy-and-cancer-risk/331896.png","ImageObject",300,407,{"name":42,"@type":43},"Anda","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-15","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What does the article mean by quasi-stochastic DNA methylation changes?","Question",{"text":63,"@type":64},"It describes age- and risk-related DNA methylation (DNAm) alterations as being acquired in a quasi-stochastic manner rather than deterministically. This stochasticity is proposed to have causal relevance in cancer development.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is DNA methylation (DNAm) defined in the paper?",{"text":68,"@type":64},"DNAm is presented as the covalent attachment of a methyl (CH3) group to cytosines, typically in a CG context denoted as CpG. For most CpG sites it is effectively binary, with a small subset showing allele-specific methylation.",{"name":70,"@type":61,"acceptedAnswer":71},"How do CpG density and CpG islands influence where DNAm changes occur?",{"text":72,"@type":64},"The article states that CpG density largely determines the direction of DNAm change, with CpG islands and low CpG-dense regions generally gaining and losing DNAm, respectively. It also notes that CpG islands overlap many gene promoters and that shore regions around islands can differ by cell type.","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},331896,1790844624,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"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":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"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,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","[royalsocietypublishing.org/journal/rstb](royalsocietypublishing.org/journal/rstb)  \nCite this article: Teschendorff AE. 2024 On epigenetic stochasticity, entropy and cancer risk. Phil. Trans. R. Soc. B 379: 20230054 .  \n[https://doi.org/10.1098/rstb.2023.0054](https://doi.org/10.1098/rstb.2023.0054)  \nReceived: 1 April 2023  \nAccepted: 26 September 2023  \nOne contribution of 10 to a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’.  \nSubject Areas:  \ngenomics, computational biology, systems biology  \nKeywords:  \nDNA methylation, stochasticity, cancer risk, ageing, epigenetic clock  \nAuthor for correspondence: Andrew E. Teschendorff  \ne-mail: [andrew@sinh.ac.cn](andrew@sinh.ac.cn)  \nOn epigenetic stochasticity, entropy and cancer risk  \n\n| Andrew E. Teschendorff |\n| --- |\n| CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, People’s Republic of China\u003Cbr> AET, 0000-0001-7410-6527 |\n| Epigenetic changes are known to accrue in normal cells as a result of ageing and cumulative exposure to cancer risk factors. Increasing evidence points towards age-related epigenetic changes being acquired in a quasi-stochastic manner, and that they may play a causal role in cancer development. Here, I describe the quasi-stochastic nature of DNA methylation (DNAm) changes in ageing cells as well as in normal cells at risk of neoplastic transformation, discussing the implications of this stochasticity for developing cancer risk prediction strategies, and in particular, how it may require a conceptual paradigm shift in how we select cancer risk markers. I also describe the mounting evidence that a significant proportion of DNAm changes in ageing and cancer development are related to cell proliferation, reflecting tissue-turnover and the opportunity this offers for predicting cancer risk via the development of epigenetic mitotic-like clocks. Finally, I describe how age-associated DNAm changes may be causally implicated in cancer development via an irreversible suppression of tissue-specific transcription factors that increases epigenetic and transcriptomic entropy, promoting amore plastic yet aberrant cancer stem-cell state.\u003Cbr>This article is part of a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’. |\n| 1. Background\u003Cbr>The word ‘stochastic’ derives from the ancient Greek στόχος (stókhos) meaning‘to take a guess’. In biological sciences it is often used to refer to biological processes that by and large appear random. One of these biological processes that has gained significant attention from the community has been the gradual ageassociated accumulation of molecular alterations in the normal cells of our bodies, which leads to cellular dysfunction and ageing [1–3] . While the main focus has been on alterations to DNA, notably somatic mutations [1], over the last decades there has been an increased interest in epigenetic alterations, including those which involve a covalent modification of DNA, known as DNA methylation (DNAm) [4–6] .\u003Cbr>DNAm refers to the covalent attachment of a methyl CH3 group to cytosines, usually, but not exclusively, in a CG context (denoted ‘CpG’ because of the phosphodiester bond) [7] . For any given CpG site in any given cell, DNAm is effectively binary (0 = both alleles unmethylated, 1 = both alleles methylated), except for a small number of loci that display allele-specific methylation (one allele methylated, the other unmethylated) . According to most recent estimates, there are about 32 million CpG sites in the human genome [8,9], with the methylation state of each CpG largely determined by its local CpG density [10]. In particular, the great majority of CpGs are relatively isolated mapping to low CpG-dense regions that are gene","cbCaim3AAGujvOgM","https://ap.wps.com/l/cbCaim3AAGujvOgM","pdf",2584011,"English","# Background\n## DNA methylation and stochastic acquisition\n## CpG density, CpG islands, and shores\n## Links between methylation, gene expression, and causality","[{\"question\":\"What does the article mean by quasi-stochastic DNA methylation changes?\",\"answer\":\"It describes age- and risk-related DNA methylation (DNAm) alterations as being acquired in a quasi-stochastic manner rather than deterministically. This stochasticity is proposed to have causal relevance in cancer development.\"},{\"question\":\"How is DNA methylation (DNAm) defined in the paper?\",\"answer\":\"DNAm is presented as the covalent attachment of a methyl (CH3) group to cytosines, typically in a CG context denoted as CpG. For most CpG sites it is effectively binary, with a small subset showing allele-specific methylation.\"},{\"question\":\"How do CpG density and CpG islands influence where DNAm changes occur?\",\"answer\":\"The article states that CpG density largely determines the direction of DNAm change, with CpG islands and low CpG-dense regions generally gaining and losing DNAm, respectively. It also notes that CpG islands overlap many gene promoters and that shore regions around islands can differ by cell type.\"}]","On epigenetic stochasticity, entropy and cancer risk | PDF",1789995651,28]