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Melanoma is a rare but aggressive malignant cancer that originates from melanocytes. These melanocytes are cells found in the basal layer of the epidermis that produce melanin under the control of melanocyte-stimulating hormone. Despite the fact that melanoma represents only a small number of all skin cancers, it is the cause of more than 50% of cancer-related deaths. The high metastatic qualities and death rate, and also its prevalence among people of younger ages have caused melanoma to become a highly researched malignant cancer. Epigenetic modifications are suspected to influence the emergence of many types of cancer-related diseases, and are also suspected to have a role in the development of melanoma. In the last few years, chemical alterations in the genome have become more evident, and these alterations can be critical in the development of malignancy. This alteration process is referred to as epigenetics (Patino et al. 2008). Epigenetics is the term used to refer to stable changes in DNA that affect gene expression but do not involve changes in the underlying nucleotide sequence of the organism (Patino et al. 2008). The mechanisms by which epigenetics occur involve hypo- and hypermethylation of DNA, histone modifications by acetylation, methylation, and phosphorylation, and posttranslational modifications which include RNA silencing. These modifications can cause different expression patterns to occur, which can result in alterations to cells. Some of these alterations could result in the formation of cancerous cells or various other dangerous changes in cell function, among many other outcomes when paired together. Cancerous cells are not formed from just one change. ==Role of cytosine methylation in melanoma== In epigenetic alterations in cancer, DNA methylation is the most studied, although it is not the only alteration that can occur. DNA methylation is a covalent modification of DNA where a methyl group is added to the C-5 position of cytosine by DNA-methyltransferases. This occurs mostly at the cytosine-phosphate-guanine dinucleotide rich regions, known as CpG islands, and are located particularly in the promoter regions of genes in the human genome (Patino et al. 2008). These promoter regions are methylated in certain ways or can be completely unmethylated. However, in an altered methylation of the CpG islands (generally where the methylation pattern is inverted), transcription can be altered which can lead to cancer. This is due to chromosomes being highly condensed, preventing RNA polymerase and other transcription factors from recognizing and binding to the DNA. This can result in gene silencing. This silencing of genes can be dangerous to cells, especially when the genes silenced are active in maintaining the cell cycle. The table below shows some of the important genes targeted by promoter hypermethylation in melanoma. TABLE 1. Various genes targeted by promoter hypermethylation in malignant melanoma Some of the genes affected by cytosine methylation in melanoma formation INK4A INK4A, also known as p16, is a tumor suppressor gene and is found to have hypermethylated promotor regions in 10- 20% of melanoma cells and is involved in 40- 87% of gene alterations in melanoma cases (Gonzalgo et al., 1997). This means that 10- 20% of the time there is an epigenetic change in the INK4A gene, and 40- 87% of the time there is a nucleotide mutation in the gene. INK4A is one of the genes that is both epigenetically and genomically altered. As a regularly functioning gene, INK4A is a tumor suppressor that functions to repress the formation of tumors. The hypermethylation of this gene can cause it to become inactivated (Straume et al., 2002). When INK4 is inactivated through hypermethylation, it causes an interruption of the CDK4 and CDK6 genes, which normally stop cell growth in the G1 phase of cell division. When this happens, there is no regulation in the cell and it grows quickly and becomes cancerous. SYK SYK is another gene that is affected by cytosine methylation during cancer progression. It is a gene that, when hypermethylated, loses function (Muthusamy et al., 2006). This gene is found in 30- 89% of melanoma cases (Dahl et al., 2007), and causes cells to grow quickly. This fast growth is important in the quick metastasis of melanoma cells, and when hypermethylated, the growth and spread of cells slow considerably (Hoeller et al., 2005). This is a controversial finding with inconclusive results, though. Some findings show that normally functioning SYK genes aids in tumor suppression, while other studies find that it is a transforming factor that facilitates cancer formation. Normally functioning, the SYK gene produces a non- receptor protein kinase enzyme that aids in differentiation, proliferation, and phagocytosis among many other important processes. SYK is found expressed in a variety of cells including fibroblasts, epithelial cells (where it controls cell division and acts as a tumor suppressor), hepatocytes, and neuronal cells (TORCIS Bioscience, 2014). Although SYK does not have any reported DNA modifications, the epigenetic changes still cause sufficient damage to cells. When SYK silencing is coupled with other alterations, both genetically and epigenetically, cancer can form. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Epigenetics and melanoma」の詳細全文を読む スポンサード リンク
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