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Melanoma is responsible for 80% of all skin cancer deaths (Miller & Mihm, 2006), and it is the most common cause of cancer deaths between the age of 20 and 35 years old (Houghton & Polsky, 2002). Melanoma is a highly heterogeneous cancer that is caused by the accumulation of genetic and epigenetic defects allowing the cell to escape normal cellular controls. Genetic changes are caused by irreversible alterations in the DNA sequence, including chromosomal amplification or deletions and gene mutations that culminate in aberrant cellular functions, such as activation of oncogenes and inactivation of tumor suppressors. However, recent progress in cancer research has shown that epigenetic events may play a major role in establishing the correct program of gene expression. Epigenetics is defined as heritable changes in gene expression that are not due to any changes in the DNA sequence. Currently, four epigenetic drugs, vorinostat (Marks & Breslow, 2007), romidepsin (Campas-Moya, 2009), azacitidine (Mani & Herceg, 2010; Wijermans et al., 2005), and decitabine (Mani & Herceg, 2010), have been approved for the treatment of hematologic malignancies in the United States by the Food and Drug Administration (U.S. FDA). In a human cell, there are approximately two meters of diploid DNA that are packaged inside the nucleus with a volume of about 1000 μm3 (Kamakaka & Biggins, 2005). This packaging of DNA is facilitated by histones. Histones are a group of highly conserved, basic (positively-charged) proteins that are rich in arginine and lysine residues. This DNA-protein complex is called the chromatin. In chromatin, proteins account for more than half of the weight, from which, histone proteins being the most abundant. There are five distinct families of histones, each with numerous variants or individual genes. DNA is packaged into nucleomes comprising a histone octamer of two copies of each core histones (H2A, H2B, H3, and H4) (Luger et al., 1997). The core histones interact in pairs. Two H3:H4 dimers interact together forming a tetramer, and two H2A:H2B dimers associate with the H3:H4 tetramer to form a nucleosome. About 146 bp of DNA is wrapped around a histone octamer. One molecule of histone H1 associates at the position where the DNA enters and exits the nucleosome core, thus sealing the two turns of DNA (Luger et al., 1997).

Epigenetic Changes in Melanoma and the Development of Epigenetic Therapy for Melanoma