Genome‐wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma. (17th April 2013)

• Record Type: Journal Article
• Authors: Gao, Linda; Smit, Marjon A.; van, Joost J.; Goeman, Jelle J.; Verdegaal, Els M. E.; van der, Sjoerd H.; Stas, Marguerite; Beck, Samuel; Gruis, Nelleke A.; Tensen, Cornelis P.; Willemze, Rein; Peeper, Daniel S.; van, Remco
• Is Part Of: Pigment cell & melanoma research. Volume 26:Number 4(2013:Jul.)
• Page Start: 542
• Page End: 554
• Publication Date: 2013-04-17
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12096
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" xml:lang="en" id="pcmr12096-abs-0001"> <title>Summary</title> <p>The involvement of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here, we performed genome‐wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic nevus interrogating 14 495 genes using BeadChip technology. This genome‐wide view of promoter methylation in primary cutaneous melanoma revealed an array of recurrent DNA methylation alterations with potential diagnostic applications. Among 106 frequently hypermethylated genes, there were many novel methylation targets and tumor suppressor genes. Highly recurrent methylation of the <italic>HOXA9</italic>, <italic> MAPK13</italic>, <italic> CDH11</italic>, <italic> PLEKHG6</italic>, <italic> PPP1R3C, </italic> and <italic>CLDN11</italic> genes was established. Promoter methylation of <italic>MAPK13</italic>, encoding p38δ, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK13 expression in melanoma cells exhibiting epigenetic silencing of this gene reduced proliferation, indicative of tumor suppressive functions. This study demonstrates that DNA methylation alterations are widespread in melanoma and suggests that epigenetic silencing of <italic>MAPK13</italic> contributes to melanoma progression.</p> </abstract>