DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Viktória Koroknai, István Szász, Hector Hernandez-Vargas, Nora Fernandez-Jimenez, Cyrille Cuenin, Zdenko Herceg, Laura Vízkeleti, Róza Ádány, Szilvia Ecsedi, Margit Balázs

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalExperimental Dermatology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Keywords

  • cell invasion
  • DNA methylation
  • gene body
  • malignant melanoma
  • TET2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Koroknai, V., Szász, I., Hernandez-Vargas, H., Fernandez-Jimenez, N., Cuenin, C., Herceg, Z., Vízkeleti, L., Ádány, R., Ecsedi, S., & Balázs, M. (Accepted/In press). DNA hypermethylation is associated with invasive phenotype of malignant melanoma. Experimental Dermatology. https://doi.org/10.1111/exd.14047