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As methylation of cancer\u2010related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (I<jats:italic>L12RB2<\/jats:italic>, <jats:italic>LYPD6B<\/jats:italic>, <jats:italic>CHL1<\/jats:italic>, <jats:italic>SLC9A3<\/jats:italic>, <jats:italic>BAALC<\/jats:italic>, <jats:italic>FAM213A<\/jats:italic>, <jats:italic>SORCS1<\/jats:italic>, <jats:italic>GPR158<\/jats:italic>, <jats:italic>FBN1<\/jats:italic> and <jats:italic>ADORA2B<\/jats:italic>) with decreased expression. On the other hand, hypermethylation in the gene body of the <jats:italic>EGFR<\/jats:italic> and <jats:italic>RBP4<\/jats:italic> genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the <jats:italic>ARHGAP22<\/jats:italic> and <jats:italic>NAV2<\/jats:italic> genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down\u2010regulation of the methylcytosine dioxygenase <jats:italic>TET2<\/jats:italic> gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells.<\/jats:p>","DOI":"10.1111\/exd.14047","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T07:23:30Z","timestamp":1570778610000},"page":"39-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["DNA hypermethylation is associated with invasive phenotype of malignant melanoma"],"prefix":"10.1111","volume":"29","author":[{"given":"Vikt\u00f3ria","family":"Koroknai","sequence":"first","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Sz\u00e1sz","sequence":"additional","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Hernandez\u2010Vargas","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer (IARC) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Fernandez\u2010Jimenez","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer (IARC) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Cuenin","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer (IARC) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenko","family":"Herceg","sequence":"additional","affiliation":[{"name":"Epigenetics Group International Agency for Research on Cancer (IARC) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"V\u00edzkeleti","sequence":"additional","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f3za","family":"\u00c1d\u00e1ny","sequence":"additional","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilvia","family":"Ecsedi","sequence":"additional","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"Epigenetics Group International Agency for Research on Cancer (IARC) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-2321","authenticated-orcid":false,"given":"Margit","family":"Bal\u00e1zs","sequence":"additional","affiliation":[{"name":"Public Health Research Institute University of Debrecen Debrecen Hungary"},{"name":"MTA\u2010DE Public Health Research Group Public Health Research Institute University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2012.01025.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/635203"},{"key":"e_1_2_9_4_1","first-page":"770","volume":"2016","author":"Paluncic J.","year":"1863","journal-title":"Biochim. 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