Azacytidine Treatment Affects Methylation Pattern of Genomic and Cell-Free DNA in Uveal Melanoma Cell Lines

Azacytidine Treatment Affects Methylation Pattern of Genomic and Cell-Free DNA in Uveal Melanoma Cell Lines | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Azacytidine Treatment Affects Methylation Pattern of Genomic and Cell-Free DNA in Uveal Melanoma Cell Lines Sarah Tadhg Ferrier, Mingyang Li, Julia V. Burnier This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4361337/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Oct, 2024 Read the published version in BMC Cancer → Version 1 posted 4 You are reading this latest preprint version Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumour in adults, and approximately 50% of patients will develop metastasis. Epigenetic changes are a major factor in cancer progression. We aimed to determine whether methylation profiles could be altered using a DNA methyltransferase (DNMT) inhibitor in UM cell lines. Methods Four primary and metastatic UM cell lines were treated with azacytidine and analysed for cell proliferation, colony formation, and BAP1 protein expression. Genomic and cfDNA methylation were compared. Results In all cell lines, azacytidine treatment resulted in a dose-dependent effects on proliferation, colony formation, and radiosensitivity. Methylation profiling revealed differences in methylation between cell lines according to BAP1 expression. Matched primary and metastatic cell lines showed very similar patterns. Alterations were seen in pathways known to be important in UM progression, such as PI3K/Akt and MAPK signaling, and in pathways involved in cancer progression, such as regulation of stemlike potential, cell motility, and invasion. These changes were maintained in genomic and cfDNA. Conclusions This data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cell-free DNA methylation could be a valuable tool. epigenetics methylation liquid biopsy cell-free DNA ctDNA Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryfiles.docx Cite Share Download PDF Status: Published Journal Publication published 21 Oct, 2024 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 24 May, 2024 Editor assigned by journal 23 May, 2024 Submission checks completed at journal 07 May, 2024 First submitted to journal 02 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4361337","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":299751261,"identity":"3ba8116a-eb76-41f7-b41d-60e069725af3","order_by":0,"name":"Sarah Tadhg Ferrier","email":"","orcid":"","institution":"Research Institute of the McGill University Health Centre","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"Tadhg","lastName":"Ferrier","suffix":""},{"id":299751262,"identity":"c8ed8a58-5b65-4dd1-9282-1968d7dae301","order_by":1,"name":"Mingyang Li","email":"","orcid":"","institution":"Research Institute of the McGill University Health Centre","correspondingAuthor":false,"prefix":"","firstName":"Mingyang","middleName":"","lastName":"Li","suffix":""},{"id":299751263,"identity":"392f19cd-6f3f-4e1b-b34d-e492c4121fde","order_by":2,"name":"Julia V. 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Epigenetic changes are a major factor in cancer progression. We aimed to determine whether methylation profiles could be altered using a DNA methyltransferase (DNMT) inhibitor in UM cell lines.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFour primary and metastatic UM cell lines were treated with azacytidine and analysed for cell proliferation, colony formation, and BAP1 protein expression. Genomic and cfDNA methylation were compared.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn all cell lines, azacytidine treatment resulted in a dose-dependent effects on proliferation, colony formation, and radiosensitivity. Methylation profiling revealed differences in methylation between cell lines according to BAP1 expression. Matched primary and metastatic cell lines showed very similar patterns. Alterations were seen in pathways known to be important in UM progression, such as PI3K/Akt and MAPK signaling, and in pathways involved in cancer progression, such as regulation of stemlike potential, cell motility, and invasion. These changes were maintained in genomic and cfDNA.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cell-free DNA methylation could be a valuable tool.\u003c/p\u003e","manuscriptTitle":"Azacytidine Treatment Affects Methylation Pattern of Genomic and Cell-Free DNA in Uveal Melanoma Cell Lines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-14 17:49:18","doi":"10.21203/rs.3.rs-4361337/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-24T08:16:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-23T10:41:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-07T13:41:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2024-05-03T00:43:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"98da5526-3022-4ca9-bf59-b0a287127caa","owner":[],"postedDate":"May 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T16:00:00+00:00","versionOfRecord":{"articleIdentity":"rs-4361337","link":"https://doi.org/10.1186/s12885-024-13037-4","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2024-10-21 15:57:14","publishedOnDateReadable":"October 21st, 2024"},"versionCreatedAt":"2024-05-14 17:49:18","video":"","vorDoi":"10.1186/s12885-024-13037-4","vorDoiUrl":"https://doi.org/10.1186/s12885-024-13037-4","workflowStages":[]},"version":"v1","identity":"rs-4361337","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4361337","identity":"rs-4361337","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}