{"data":{"id":"10.6084/m9.figshare.1497885","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1497885","prefix":"10.6084","suffix":"m9.figshare.1497885","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"G Malouf, Gabriel","givenName":"Gabriel","familyName":"G Malouf","affiliation":[],"nameIdentifiers":[]},{"name":"Tahara, Tomomitsu","givenName":"Tomomitsu","familyName":"Tahara","affiliation":[],"nameIdentifiers":[]},{"name":"Paradis, Valérie","givenName":"Valérie","familyName":"Paradis","affiliation":[],"nameIdentifiers":[]},{"name":"Fabre, Monique","givenName":"Monique","familyName":"Fabre","affiliation":[],"nameIdentifiers":[]},{"name":"Guettier, Catherine","givenName":"Catherine","familyName":"Guettier","affiliation":[],"nameIdentifiers":[]},{"name":"Yamazaki, Jumpei","givenName":"Jumpei","familyName":"Yamazaki","affiliation":[],"nameIdentifiers":[]},{"name":"Long, Hi","givenName":"Hi","familyName":"Long","affiliation":[],"nameIdentifiers":[]},{"name":"Lu, Yue","givenName":"Yue","familyName":"Lu","affiliation":[],"nameIdentifiers":[]},{"name":"J-M Raynal, Noël","givenName":"Noël","familyName":"J-M Raynal","affiliation":[],"nameIdentifiers":[]},{"name":"Jelinek, Jaroslav","givenName":"Jaroslav","familyName":"Jelinek","affiliation":[],"nameIdentifiers":[]},{"name":"Mouawad, Roger","givenName":"Roger","familyName":"Mouawad","affiliation":[],"nameIdentifiers":[]},{"name":"Khayat, David","givenName":"David","familyName":"Khayat","affiliation":[],"nameIdentifiers":[]},{"name":"Brugières, Laurence","givenName":"Laurence","familyName":"Brugières","affiliation":[],"nameIdentifiers":[]},{"name":"Raymond, Eric","givenName":"Eric","familyName":"Raymond","affiliation":[],"nameIdentifiers":[]},{"name":"J Issa, Jean-Pierre","givenName":"Jean-Pierre","familyName":"J Issa","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Environmental Sciences not elsewhere classified"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Biological Sciences not elsewhere classified"},{"subject":"Developmental Biology"},{"subject":"Cancer"},{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Plant Biology"}],"contributors":[],"dates":[{"date":"2015-10-20","dateType":"Created"},{"date":"2023-06-01","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15592294.2015.1076955","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["8882087 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"With the goal of studying epigenetic alterations in fibrolamellar hepatocellular carcinoma (FLC) and establish an associated DNA methylation signature, we analyzed \u003ci\u003eLINE-1\u003c/i\u003e methylation in a cohort of FLC and performed next-generation sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene expression. Furthermore, we established and validated an epigenetic signature differentiating pure-FLC from other HCCs. \u003ci\u003eLINE-1\u003c/i\u003e methylation correlated with shorter recurrence-free survival and overall survival in resected pure-FLC patients. Unsupervised clustering using CG sites located in islands distinguished pure-FLC from nc-HCC. Major DNA methylation changes occurred outside promoters, mainly in gene bodies and intergenic regions located in the vicinity of liver developmental genes (i.e., \u003ci\u003eSMARCA4\u003c/i\u003e and \u003ci\u003eRXRA\u003c/i\u003e). Partially methylated domains were more prone to DNA methylation changes. Furthermore, we identified several putative tumor suppressor genes (e.g., \u003ci\u003eDLEU7\u003c/i\u003e) and oncogenes (e.g., \u003ci\u003eDUSP4\u003c/i\u003e). While ∼70% of identified gene promoters gaining methylation were marked by bivalent histone marks (H3K4me3/H3K27me3) in embryonic stem cells, ∼70% of those losing methylation were marked by H3K4me3. Finally, we established a pure FLC DNA methylation signature and validated it in an independent dataset. Our analysis reveals a distinct epigenetic signature of pure FLC as compared to nc-HCC, with DNA methylation changes occurring in the vicinity of liver developmental genes. These data suggest new options for targeting FLC based on cancer epigenome 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