DNA methylation subgroups in melanoma are associated with proliferative and immunological processes

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Abstract

Background: DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity. Methods: We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data. Results: We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes. Conclusions: Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.

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Lauss, M., Ringnér, M., Karlsson, A., Harbst, K., Busch, C., Geisler, J., … Jönsson, G. (2015). DNA methylation subgroups in melanoma are associated with proliferative and immunological processes. BMC Medical Genomics, 8(1). https://doi.org/10.1186/s12920-015-0147-4

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