Epigenetic mechanisms such as promoter methylation affect gene expression by inducing changes in organizational structure of chromatin rather than in the DNA sequence. Increased methylation of... Show moreEpigenetic mechanisms such as promoter methylation affect gene expression by inducing changes in organizational structure of chromatin rather than in the DNA sequence. Increased methylation of cytosine within cystosine-guanine (CpG) dinucleotides that are located at higher density in gene promoter regions is associated with transcriptional silencing, and has been found in various cancer types. In cutaneous melanoma, a type of skin cancer that originates from pigment-producing cells, aberrant increase in promoter methylation together with inactivation of gene expression has also been observed. The aim of this thesis was to characterize promoter methylation patterns of primary cutaneous melanomas and common naevi on a genome-wide scale, in order to identify epigenetic alterations that are important in the development of melanoma and that may serve as potential diagnostic or prognostic biomarkers. Methylation profiling of 27,578 CpG loci across 14,495 genes identified frequent epigenetic inactivation of MAPK13 affecting melanoma cell proliferation; RASEF was identified as an essential component in oncogene-induced senescence, consistent with a tumor-suppressive role in melanoma. CLDN11 methylation was found to have diagnostic value in distinguishing melanoma from benign melanocytic lesions. Additionally we observed that SYNPO2 promoter hypermethylation and diminished gene expression had significant effect on melanoma-specific survival of patients. Show less
