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Genome‐wide promoter methylation analysis identifies epigenetic silencing of MAPK 13 in primary cutaneous melanoma
Author(s) -
Gao Linda,
Smit Marjon A.,
den Oord Joost J.,
Goeman Jelle J.,
Verdegaal Els M. E.,
Burg Sjoerd H.,
Stas Marguerite,
Beck Samuel,
Gruis Nelleke A.,
Tensen Cornelis P.,
Willemze Rein,
Peeper Daniel S.,
Doorn Remco
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12096
Subject(s) - epigenetics , dna methylation , biology , methylation , gene silencing , melanoma , cancer research , gene , genetics , microbiology and biotechnology , gene expression
Summary 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 HOXA 9 , MAPK 13 , CDH 11 , PLEKHG 6 , PPP 1R3C, and CLDN 11 genes was established. Promoter methylation of MAPK 13 , encoding p38δ, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK 13 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 MAPK 13 contributes to melanoma progression.