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While DNA 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) have been studied extensively in malignant tumors, their roles in early progression remain unclear. This study quantifies genome-wide dynamics of 5hmC and 5mC across lesion stages, links changes to transcription start site activity, and evaluates TET2-related demethylation mechanisms and potential biomarker relevance.",{"@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/genome-wide-characterization-of-dynamic-dna-5-hydroxymethylcytosine-and-tet2-related-dna-demethylation-during-breast-tumorigenesis/333765/",{"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/genome-wide-characterization-of-dynamic-dna-5-hydroxymethylcytosine-and-tet2-related-dna-demethylation-during-breast-tumorigenesis/333765.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How do DNA 5hmC and 5mC change across breast tumorigenesis stages?","Question",{"text":112,"@type":113},"They decrease significantly from usual ductal hyperplasia through atypical ductal hyperplasia and then to ductal carcinoma in situ, with a modest increase in invasive ductal breast cancer compared to DCIS.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Where do the 5hmC and 5mC changes mainly occur and how are they related to gene expression?",{"text":117,"@type":113},"The genomic changes occur around transcription start sites, and the modification levels strongly correlate with gene expression levels.",{"name":119,"@type":110,"acceptedAnswer":120},"What role is suggested for TET2-related DNA demethylation and transcription factors?",{"text":121,"@type":113},"TET2-related DNA demethylation appears involved in breast tumorigenesis, and four transcription factor binding sites (ESR1, FOXA1, GATA3, FOS) are enriched in TET2-related differentially hydroxymethylated/methylated regions.","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},333765,1790197296,{"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":29,"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},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Wu et al. Clinical Epigenetics (2024) 16:125 [https://doi.org/10.1186/s13148-024-01726-7](https://doi.org/10.1186/s13148-024-01726-7)  \nClinical Epigenetics  \n RESEARCH Open Access  \nGenome-wide characterization of dynamic   DNA 5-hydroxymethylcytosine and TET2-related  \nDNA demethylation during breast tumorigenesis  \nShuang-Ling Wu1,2†, Lin Yang2†, Changcai Huang3†, Qing Li2, Chunhui Ma2, Fang Yuan4, Yinglin Zhou5, Xiaoyue Wang6, Wei-Min Tong2,7, Yamei Niu2,7* and Feng Jin1*  \nAbstract  \nBackground Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous.  \nResults DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS) . However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmCand 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched inTET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cellfree DNA (cfDNA) .  \nConclusions Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved inTET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening. Keywords Breast tumorigenesis, DNA 5-hydroxymethylcytosine, 5-methylcytosine, DNA methylation, DNA demethylation, TET2, cfDNA  \n†Shuang-Ling Wu, Lin Yang and Changcai Huang contributed equally to this work.  \n*Correspondence:  \nYamei Niu [niuym@ibms.pumc.edu.cn](niuym@ibms.pumc.edu.cn)[ ](niuym@ibms.pumc.edu.cn)Feng Jin [jinfeng@cmu.edu.cn](jinfeng@cmu.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a 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-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nWu et al. Clinical Epigenetics (2024) 16:125  \nBackground  \nBreast cancer is the most prevalent cancer worldwide [1, 2] . Epidemiological and pathological studies have shown that breast tumorigenesis is a ","cbCaijPBqcYQNm42","https://ap.wps.com/l/cbCaijPBqcYQNm42","pdf",4032238,21,"English","# Abstract\n## Background\n## Results\n## Conclusions\n# Background\n## Breast cancer progression and need for biomarkers\n## DNA methylation/demethylation and 5hmC/cfDNA context","[{\"question\":\"How do DNA 5hmC and 5mC change across breast tumorigenesis stages?\",\"answer\":\"They decrease significantly from usual ductal hyperplasia through atypical ductal hyperplasia and then to ductal carcinoma in situ, with a modest increase in invasive ductal breast cancer compared to DCIS.\"},{\"question\":\"Where do the 5hmC and 5mC changes mainly occur and how are they related to gene expression?\",\"answer\":\"The genomic changes occur around transcription start sites, and the modification levels strongly correlate with gene expression levels.\"},{\"question\":\"What role is suggested for TET2-related DNA demethylation and transcription factors?\",\"answer\":\"TET2-related DNA demethylation appears involved in breast tumorigenesis, and four transcription factor binding sites (ESR1, FOXA1, GATA3, FOS) are enriched in TET2-related differentially hydroxymethylated/methylated regions.\"}]","Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis | PDF",1790003939,53]