期刊
EXPERIMENTAL DERMATOLOGY
卷 29, 期 1, 页码 39-50出版社
WILEY
DOI: 10.1111/exd.14047
关键词
cell invasion; DNA methylation; gene body; malignant melanoma; TET2
类别
资金
- National Research Development and Innovation Fund [K112327]
- New National Excellence Programme of the Ministry of Human Capacities [UNKP-18-3]
- IARC Postdoctoral Fellowship
- Marie Curie Actions-People-COFUND
- European Union under the European Social Fund
- European Regional Development Fund [GINOP-2.3.2-15-2016-00005]
- EC
- Association pour la Recherche sur le Cancer (ARC), France
- la Ligue Nationale (Francaise) Contre le Cancer, France
Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related 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 (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 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 ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 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.
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