Melanoma, also called cutaneous melanoma or malignant melanoma, is a type of skin cancer that begins in melanocytes and usually occurs in areas that are exposed to the sun. Melanoma is usually cutaneous, but in about 5% of cases it develops in the melanocytes of other tissues, including the eyes or mucous membranes.

Frequently, melanomas have irregular borders and an irregular shape. They can vary from a few millimeters to several centimeters in width. They can also be of a variety of colors: brown, black, red, pink, blue or white. In addition, most melanomas affect only the epidermis; although it can extend to other parts of the body. Melanoma is also a common feature of the genetic syndromes that affect the skin, such as xeroderma pigmentosum and Gorlin syndrome. In addition, people who have previously had melanoma are almost nine times more likely than the general population to develop melanoma again.

This process is due to a combination of environmental and genetic factors. The greatest environmental risk factor for developing melanoma is exposure to ultraviolet radiation from the sun and tanning beds, because it damages DNA. Most of the time, this type of DNA damage causes the cells to suffer apoptosis or senescence. However, melanocytes are more resistant than other types of cells to the effects of UV radiation. Even if your DNA is damaged, it is unlikely that melanocytes will experience apoptosis. As the abnormal melanocytes continue to grow, they accumulate genetic mutations, particularly in the genes that control cell growth and proliferation, senescence, and apoptosis. Ultimately, the cells become able to proliferate without control or limit and can resist cell death, leading to the formation and growth of a melanoma.

Most cases of melanoma are not hereditary and are due to somatic mutations that are acquired during the life of a person and are present only in the melanocytes that give rise to melanoma. Studies suggest that in some cases somatic variations in multiple genes, each with a small effect, combine to increase the risk of developing the disease. Other somatic genetic mutations have large effects on the risk of melanoma and a mutation in one gene is enough to significantly increase the risk of developing cancer. Somatic mutations in the BRAF (B-Raf proto-oncogene, serine / threonine kinase), located on the long arm of chromosome 7 (7q34) and CDKN2A (cyclin dependent kinase inhibitor 2A), located on the short arm of chromosome 9 (9p21.3) genes, are some of the most frequent in sporadic melanoma.

In about 10 percent of cases, melanoma is due to inherited genetic changes that increase the risk of developing this type of cancer. These genetic changes are present in virtually every cell in the body. The main genes involved in familial melanoma are the CDKN2A gene (cyclin dependent kinase inhibitor 2A) and the MC1R gene (melanocortin 1 receptor). The CDKN2A gene plays a role in the regulation of cellular senescence and the MC1R gene influences the pigmentation of the skin.

Other genes identified, whose mutations increase the risk of developing melanoma include: ASIP, ATM, BAP1, CASP8, CDK4, CDK10, EGF, HERC2, IRF4, KITLG, MITF, MTAP, MX2, MYH7B, NRAS, OCA2, PIGU, PLA2G6, POT1, SLC2A4, SLC45A2, TERT, TP53, TPCN2, TYR, TYRP1, XRCC3 genes.