{"data":{"id":"10.6084/m9.figshare.1295513.v2","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1295513.v2","prefix":"10.6084","suffix":"m9.figshare.1295513.v2","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Hallberg, Andrea R","nameType":"Personal","givenName":"Andrea R","familyName":"Hallberg","affiliation":[],"nameIdentifiers":[]},{"name":"Vorrink, Sabine U","nameType":"Personal","givenName":"Sabine U","familyName":"Vorrink","affiliation":[],"nameIdentifiers":[]},{"name":"Hudachek, Danielle R","nameType":"Personal","givenName":"Danielle R","familyName":"Hudachek","affiliation":[],"nameIdentifiers":[]},{"name":"Cramer-Morales, Kimberly","nameType":"Personal","givenName":"Kimberly","familyName":"Cramer-Morales","affiliation":[],"nameIdentifiers":[]},{"name":"Milhem, Mohammed M","nameType":"Personal","givenName":"Mohammed M","familyName":"Milhem","affiliation":[],"nameIdentifiers":[]},{"name":"Cornell, Robert A","nameType":"Personal","givenName":"Robert A","familyName":"Cornell","affiliation":[],"nameIdentifiers":[]},{"name":"Domann, Frederick E","nameType":"Personal","givenName":"Frederick E","familyName":"Domann","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Aberrant CpG methylation of the \u003ci\u003eTFAP2A\u003c/i\u003e gene constitutes a mechanism for loss of \u003ci\u003eTFAP2A\u003c/i\u003e expression in human metastatic melanoma"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Hematology"},{"subject":"111714 Mental Health","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"subject":"Chemistry"},{"subject":"Physiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"Medicine"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-10-20","dateType":"Created"},{"date":"2016-01-19","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":"10.4161/15592294.2014.988062","relatedIdentifierType":"DOI"},{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.1295513","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["0 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":"Metastatic melanoma is a deadly treatment-resistant form of skin cancer whose global incidence is on the rise. During melanocyte transformation and melanoma progression the expression profile of many genes changes. Among these, a gene implicated in several steps of melanocyte development, \u003ci\u003eTFAP2A\u003c/i\u003e, is frequently silenced; however, the molecular mechanism of \u003ci\u003eTFAP2A\u003c/i\u003e silencing in human melanoma remains unknown. In this study, we measured \u003ci\u003eTFAP2A\u003c/i\u003e mRNA expression in primary human melanocytes compared to 11 human melanoma samples by quantitative real-time RT-PCR. In addition, we assessed CpG DNA methylation of the \u003ci\u003eTFAP2A\u003c/i\u003e promoter in these samples using bisulfite sequencing. Compared to primary melanocytes, which showed high \u003ci\u003eTFAP2A\u003c/i\u003e mRNA expression and no promoter methylation, human melanoma samples showed decreased \u003ci\u003eTFAP2A\u003c/i\u003e mRNA expression and increased promoter methylation. We further show that increased CpG methylation correlates with decreased \u003ci\u003eTFAP2A\u003c/i\u003e mRNA expression. Using The Cancer Genome Atlas, we further identified \u003ci\u003eTFAP2A\u003c/i\u003e as a gene displaying among the most decreased expression in stage 4 melanomas vs. non-stage 4 melanomas, and whose CpG methylation was frequently associated with lack of mRNA expression. Based on our data, we conclude that \u003ci\u003eTFAP2A\u003c/i\u003e expression in human melanomas can be silenced by aberrant CpG methylation of the \u003ci\u003eTFAP2A\u003c/i\u003e promoter. We have identified aberrant CpG DNA methylation as an epigenetic mark associated with TFAP2A silencing in human melanoma that could have significant implications for the therapy of human melanoma using epigenetic modifying drugs.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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