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In orbitofacial neurofibromatosis type 1, NFs may cause progressive, disfiguring tumors of the lid, brow, temple, face and orbit. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We used Illumina Methylation EPIC BeadChip to study DNA methylation differences between orbitofacial NFs (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u200920) and NFs at other sites (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u20094). Global methylation differences were detected between the two groups and the top differentially methylated genes were part of the\n                    <jats:italic>HOX\u00a0(Homebox)<\/jats:italic>\n                    family of transcription factors (\n                    <jats:italic>HOXC8, HOXC4, HOXC6, HOXA6 and HOXD4<\/jats:italic>\n                    ), which were hypomethylated in orbitofacial NFs compared to the non-orbital NFs. Conversely,\n                    <jats:italic>LTF<\/jats:italic>\n                    (lactoferrin) was relatively hypermethylated in orbitofacial NF compared to non-orbitofacial NF. HOXC8 protein levels were higher in orbitofacial plexiform NFs (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u20090.04). We found no significant differences in the expression of\n                    <jats:italic>HOXC4, HOXA6, or HOXD4<\/jats:italic>\n                    between the two groups.\n                    <jats:italic>HOXC8<\/jats:italic>\n                    mRNA levels were also higher in orbitofacial NFs and\n                    <jats:italic>HOXC8<\/jats:italic>\n                    overexpression in a non-neoplastic human Schwann cell line resulted in increased growth. In summary, we identified gene methylation and expression differences between orbitofacial NF and NFs occurring at other locations. Further investigation may be warranted, given that the\n                    <jats:italic>HOX<\/jats:italic>\n                    family of genes play an important role during development, are dysregulated in a variety of cancers, and may provide novel insights into therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1186\/s40478-020-00940-7","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T05:02:38Z","timestamp":1588568558000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Differential gene methylation and expression of HOX transcription factor family in orbitofacial neurofibroma"],"prefix":"10.1186","volume":"8","author":[{"given":"Antje","family":"Arnold","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddie Luidy","family":"Imada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8029-4787","authenticated-orcid":false,"given":"M. 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