Title: Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma
Authors: Gao, Linda ×
Smit, Marjon A
van den Oord, Joost
Goeman, Jelle J
Verdegaal, Els M E
van der Burg, Sjoerd H
Stas, Marguerite
Beck, Samuel
Gruis, Nelleke A
Tensen, Cornelis P
Willemze, Rein
Peeper, Daniel S
van Doorn, Remco #
Issue Date: Jul-2013
Publisher: Wiley-Blackwell Publishing, Inc
Series Title: Pigment Cell & Melanoma Research vol:26 issue:4 pages:542-54
Article number: 10.1111/pcmr.12096
Abstract: 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 HOXA9, MAPK13, CDH11, PLEKHG6, PPP1R3C, and CLDN11 genes was established. Promoter methylation of MAPK13, 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 MAPK13 contributes to melanoma progression.
ISSN: 1755-1471
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Surgical Oncology
× corresponding author
# (joint) last author

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