{"data":{"id":"10.6084/m9.figshare.c.2096102","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2096102","prefix":"10.6084","suffix":"m9.figshare.c.2096102","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":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"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 aberrations.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjQvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLkMuMjA5NjEwMjwvaWRlbnRpZmllcj4KICA8Y3JlYXRvcnM+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkdhYnJpZWwgRyBNYWxvdWY8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkdhYnJpZWw8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+RyBNYWxvdWY8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlRvbW9taXRzdSBUYWhhcmE8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPlRvbW9taXRzdTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5UYWhhcmE8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlZhbMOpcmllIFBhcmFkaXM8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPlZhbMOpcmllPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPlBhcmFkaXM8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPk1vbmlxdWUgRmFicmU8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPk1vbmlxdWU8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+RmFicmU8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkNhdGhlcmluZSBHdWV0dGllcjwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+Q2F0aGVyaW5lPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkd1ZXR0aWVyPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5KdW1wZWkgWWFtYXpha2k8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkp1bXBlaTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5ZYW1hemFraTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+SGkgTG9uZzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+SGk8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+TG9uZzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+WXVlIEx1PC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5ZdWU8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+THU8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPk5vw6tsIEotTSBSYXluYWw8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPk5vw6tsPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkotTSBSYXluYWw8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkphcm9zbGF2IEplbGluZWs8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkphcm9zbGF2PC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkplbGluZWs8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlJvZ2VyIE1vdWF3YWQ8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPlJvZ2VyPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPk1vdWF3YWQ8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkRhdmlkIEtoYXlhdDwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+RGF2aWQ8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+S2hheWF0PC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5MYXVyZW5jZSBCcnVnacOocmVzPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5MYXVyZW5jZTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5CcnVnacOocmVzPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5FcmljIFJheW1vbmQ8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkVyaWM8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+UmF5bW9uZDwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+SmVhbi1QaWVycmUgSiBJc3NhPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5KZWFuLVBpZXJyZTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5KIElzc2E8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgPC9jcmVhdG9ycz4KICA8dGl0bGVzPgogICAgPHRpdGxlPk1ldGh5bG9tZSBzZXF1ZW5jaW5nIGZvciBmaWJyb2xhbWVsbGFyIGhlcGF0b2NlbGx1bGFyIGNhcmNpbm9tYSBkZXBpY3RzIGRpc3RpbmN0aXZlIGZlYXR1cmVzPC90aXRsZT4KICA8L3RpdGxlcz4KICA8ZGVzY3JpcHRpb25zPgogICAgPGRlc2NyaXB0aW9uIGRlc2NyaXB0aW9uVHlwZT0iQWJzdHJhY3QiPiZsdDtwJmd0O1dpdGggdGhlIGdvYWwgb2Ygc3R1ZHlpbmcgZXBpZ2VuZXRpYyBhbHRlcmF0aW9ucyBpbiBmaWJyb2xhbWVsbGFyIGhlcGF0b2NlbGx1bGFyIGNhcmNpbm9tYSAoRkxDKSBhbmQgZXN0YWJsaXNoIGFuIGFzc29jaWF0ZWQgRE5BIG1ldGh5bGF0aW9uIHNpZ25hdHVyZSwgd2UgYW5hbHl6ZWQgJmx0O2kmZ3Q7TElORS0xJmx0Oy9pJmd0OyBtZXRoeWxhdGlvbiBpbiBhIGNvaG9ydCBvZiBGTEMgYW5kIHBlcmZvcm1lZCBuZXh0LWdlbmVyYXRpb24gc2VxdWVuY2luZyBvZiBETkEgbWV0aHlsYXRpb24gaW4gYSB0cmFpbmluZyBzZXQgb2YgcHVyZS1GTENzIGFuZCBub24tY2lycmhvdGljIGhlcGF0b2NlbGx1bGFyIGNhcmNpbm9tYXMgKG5jLUhDQykuIEROQSBtZXRoeWxhdGlvbiB3YXMgY29ycmVsYXRlZCB3aXRoIGdlbmUgZXhwcmVzc2lvbi4gRnVydGhlcm1vcmUsIHdlIGVzdGFibGlzaGVkIGFuZCB2YWxpZGF0ZWQgYW4gZXBpZ2VuZXRpYyBzaWduYXR1cmUgZGlmZmVyZW50aWF0aW5nIHB1cmUtRkxDIGZyb20gb3RoZXIgSENDcy4gJmx0O2kmZ3Q7TElORS0xJmx0Oy9pJmd0OyBtZXRoeWxhdGlvbiBjb3JyZWxhdGVkIHdpdGggc2hvcnRlciByZWN1cnJlbmNlLWZyZWUgc3Vydml2YWwgYW5kIG92ZXJhbGwgc3Vydml2YWwgaW4gcmVzZWN0ZWQgcHVyZS1GTEMgcGF0aWVudHMuIFVuc3VwZXJ2aXNlZCBjbHVzdGVyaW5nIHVzaW5nIENHIHNpdGVzIGxvY2F0ZWQgaW4gaXNsYW5kcyBkaXN0aW5ndWlzaGVkIHB1cmUtRkxDIGZyb20gbmMtSENDLiBNYWpvciBETkEgbWV0aHlsYXRpb24gY2hhbmdlcyBvY2N1cnJlZCBvdXRzaWRlIHByb21vdGVycywgbWFpbmx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