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Using the Infinium Methylation EPIC BeadChip interrogating >850,000 CpG sites, evDNA and nuclear DNA showed strong concordance across cell lines and clinical samples. The results support evDNA as a noninvasive surrogate for tissue origin and as a promising biomarker for cancer diagnostics, enabling methylation-based deconvolution in heterogeneous populations.",{"@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 & 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question does the study address about extracellular vesicle-derived DNA?","Question",{"text":63,"@type":64},"It tests whether evDNA methylation patterns mirror the epigenetic features of the parental genomic DNA from which the vesicles originate.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the DNA methylation analysis performed?",{"text":68,"@type":64},"The study isolated evDNA secreted by cancer cell lines and evDNA/nuclear DNA from primary cancer tissues, then carried out genome-wide methylation analysis using the Infinium Methylation EPIC BeadChip covering more than 850,000 CpG sites.",{"name":70,"@type":61,"acceptedAnswer":71},"What did the study find when comparing evDNA and nuclear DNA methylation patterns?",{"text":72,"@type":64},"Remarkable similarities were observed between evDNA and nuclear DNA methylation patterns in cancer cell lines and in clinical cancer tissue 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nature.com/scientificreports)  \nOPEN  \nGenome-wide methylation profiling reveals extracellular vesicle DNA as an ex vivo surrogate of cancer cell-derived DNA  \nKyung-A Kim1,2,8, Sunmin Kim3,4,5,8, Inbal Wortzel6,8, Suho Lee1, Yoon Dae Han7, Tae-Min Kim3,4,5􀀍 & Han Sang Kim1,2􀀍  \nExtracellular vesicle-derived DNA (evDNA) encapsulates the complete genome and mutational status of cells; however, whether cancer cell-derived evDNA mirrors the epigenetic features of parental genomic DNA remains uncertain. This study aimed to assess and compare the DNA methylation patterns of evDNA from cancer cell lines and primary cancer tissues with those of the nuclear genomic DNA. We isolated evDNA secreted by two cancer cell lines (HCT116 and MDA-MB-231) from various subcellular compartments, includingthe nucleus and cytoplasm. Additionally, we obtained evDNA and nuclear DNA (nDNA) from the primary cancer tissues of colon cancer patients. We conducted a comprehensive genome-wide DNA methylation analysis using the Infinium Methylation EPIC BeadChip, examining > 850,000 CpG sites. Remarkable similarities were observed between evDNA and nDNA methylation patterns in cancer cell lines and patients. This concordance extended to clinical cancer tissue samples, showcasing the potential utility of evDNA methylation patterns in deducing cellular origin within heterogeneous populations through methylation-based deconvolution. The observed concordance underscores the potential of evDNA as a noninvasive surrogate marker for discerning tissue origin, particularly in cancer tissues, offering a promising future for cancer diagnostics. This finding enhances our understanding of cellular origins and would help develop innovative diagnostic and therapeutic strategies for cancer.  \nKeywords DNA methylation, Extracellular vesicles, Exosome, EV-DNA, Epigenetic modifications, Cancer  \nEpigenetic alterations are considered among the earliest genomic changes in carcinogenesis1. DNA methylation, a crucial epigenetic process, primarily occurs at cytosine bases within cytosine-guanine dinucleotides (CpGs)2. It plays a pivotal role in regulating several cellular processes, such as gene expression, genomic imprinting, and maintaining genomic stability3,4. Cancer is often characterized by distinct aberrant DNA methylation patterns5,6, involving widespread hypomethylation and localized hypermethylation of specific genomic regions7,8. The stability and detectability of DNA methylation across various sample types, including tumor tissues and body fluids, further underscore its significance9–11. Accordingly, leveraging DNA methylation patterns as biomarkers has emerged as a promising strategy for improving cancer diagnosis12.  \nExtracellular vesicles (EVs), membrane-bound entities with 30–150 nm size, are released by virtually all cell types and are ubiquitous in bodily fluids13. They play a crucial role in intercellular communication by transferring various cellular constituents into recipient cells14–16. Accumulating evidence establishes a connection between  \n1Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea. 2Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemungu, Seoul 03722, Republic of Korea. 3Department of Medical Informatics, College of Medicine, Catholic University of Korea, 222, BanpoDaero, Seocho-Gu, Seoul 06591, Republic of Korea. 4College of Medicine, Cancer Research Institute, The Catholic University of Korea, Seoul, Republic of Korea. 5Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea. 6Children’s Cancer and Blood Foundation Laboratories, Department of Pediatrics, Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer C","cbCaio0L2UKRJD5Z","https://ap.wps.com/l/cbCaio0L2UKRJD5Z","pdf",4317431,13,"English","# Results\n## Characterization of EVs and subcellular fractions","[{\"question\":\"What question does the study address about extracellular vesicle-derived DNA?\",\"answer\":\"It tests whether evDNA methylation patterns mirror the epigenetic features of the parental genomic DNA from which the vesicles originate.\"},{\"question\":\"How was the DNA methylation analysis performed?\",\"answer\":\"The study isolated evDNA secreted by cancer cell lines and evDNA/nuclear DNA from primary cancer tissues, then carried out genome-wide methylation analysis using the Infinium Methylation EPIC BeadChip covering more than 850,000 CpG sites.\"},{\"question\":\"What did the study find when comparing evDNA and nuclear DNA methylation patterns?\",\"answer\":\"Remarkable similarities were observed between evDNA and nuclear DNA methylation patterns in cancer cell lines and in clinical cancer tissue samples.\"}]","Genome-wide methylation profiling reveals extracellular vesicle DNA as an ex vivo surrogate of cancer cell-derived DNA | PDF",1789998932,33]