Åke Borg
Principal investigator
Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation.
Author
Summary, in English
The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development and a lineage-specific oncogene in melanoma; a highly lethal cancer known for its unpredictable clinical course. MITF is regulated by multiple intracellular signaling pathways although the exact mechanisms that determine MITF expression and activity remain incompletely understood. In this study, we obtained genome-wide DNA methylation profiles from 50 stage IV melanomas, normal melanocytes, keratinocytes and dermal fibroblasts, and utilized The Cancer Genome Atlas (TCGA) data for experimental validation. By integrating DNA methylation and gene expression data we found that hypermethylation of MITF and its co-regulated differentiation pathway genes, corresponded to decreased gene expression levels. In cell lines with a hypermethylated MITF-pathway, over-expression of MITF did not alter the expression level or methylation status of the MITF pathway genes. In contrast however, demethylation treatment of these cell lines induced MITF-pathway activity, confirming that gene-regulation was controlled via methylation. The discovery that the activity of the master regulator of pigmentation, MITF, and its downstream targets may be regulated by hypermethylation has significant implications for understanding the development and evolvement of melanoma.Journal of Investigative Dermatology accepted article preview online, 23 February 2015. doi:10.1038/jid.2015.61.
Department/s
- Melanoma Genomics
- Breastcancer-genetics
- Create Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Tumor microenvironment
Publishing year
2015
Language
English
Pages
1820-1828
Publication/Series
Journal of Investigative Dermatology
Volume
135
Issue
7
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Dermatology and Venereal Diseases
Status
Published
Research group
- Melanoma Genomics
ISBN/ISSN/Other
- ISSN: 1523-1747