This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Malignant Melanoma
Malignant melanoma is the most dangerous skin cancer and is the leading cause of death due to skin disease. According to the National Cancer Institute, there will be an estimated 76,250 new cases of melanoma in the United States in 2012. An estimated 9,180 of these cases will result in death. When found early, recovery rates from melanoma are relatively high. When found in advanced stages, however, it can be very difficult to win the battle against malignant melanoma.
Melanoma is cancer that develops in melanocytes, a particular kind of skin cell. Melanocytes produce skin pigment, which is why many melanomas are dark in color. Melanocytes are found in the epidermis, which is the outermost layer of skin. Melanomas can be found on many areas of the skin. According to PubMed Health, melanomas are commonly found on arms, legs, neck, face, and the trunk region, but can be found in rare places such as the eye, esophagus, mouth, vagina, and urinary tract. Melanomas can develop from pre-existing moles, also called a nevus or multiple nevi, or can appear as new marks.
Melanoma is cancer that develops in melanocytes, a particular kind of skin cell. Melanocytes produce skin pigment, which is why many melanomas are dark in color. Melanocytes are found in the epidermis, which is the outermost layer of skin. Melanomas can be found on many areas of the skin. According to PubMed Health, melanomas are commonly found on arms, legs, neck, face, and the trunk region, but can be found in rare places such as the eye, esophagus, mouth, vagina, and urinary tract. Melanomas can develop from pre-existing moles, also called a nevus or multiple nevi, or can appear as new marks.
ABCDEs of Melanoma
The American Academy of Dermatology has published an easy to remember self-assessment system to check moles for potential melanoma development. It is called the ABCDEs of melanoma. If you feel that a mole has these characteristics you should contact a dermatologist.
Asymmetry Border Color Diameter Evolving |
Risk Factors for Melanoma
There are multiple environmental and other non-genetic risk factors that are associated with an increase in melanoma development. They include:
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CDKN2A
CDKN2A, or cyclin-dependent kinase inhibitor 2A, is the primary gene associated with malignant melanoma susceptibility. CDKN2A is a tumor suppressor gene found on the short arm of chromosome 9. It goes by many names such as the protein it encodes, p16, as well other names including MLM, INK4, and MTS1. Normally, the gene functions to halt tumor development by arresting the cell cycle at the G1/S checkpoints. As explained by the National Cancer Institute, a mutation in this gene leading to the loss of its function is responsible for the the development of malignant melanoma in just under half of the familial melanoma cases. In 2011, there had been at least 30 distinct germline mutations of CDKN2A associated with familial melanoma identified. Germline mutations of CDKN2A are associated with an increase in nevi observed in some families. These mutations occur in a variety of different forms such as large deletions and nonsense mutations.
References
Bishop, DT et al. (2009). Genome-wide association study identifies three loci associated with melanoma risk. Nature Genetics, 41(8), 920-5.
doi: 10.1038/ng.411.
Cabanillas, Rubén et al. (2011). Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas. Head and Neck. doi: 10.1002/hed.21911
Lesueur, F et al. (2008). The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. British Journal of Cancer. 99(2), 364-70. doi: 10.1038/sj.bjc.6604470
Miller, A et al. (2006). Melanoma. The New England Journal of Medicine. 355(1), 51-65. PMID:16822996
Nikolaou, V et al. (2011). Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. British Journal of Dermatology, 165(6), 1219-22. doi: 10.1111/j.1365-2133.2011.10551.x
Reginster, M et al. (2011). Molecular Dermapathology in Malignant Melanoma. Dermatology Research and Practice. 2012(684032). doi:10.1155/2012/684032
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001853/
http://www.aad.org/skin-conditions/dermatology-a-to-z/melanoma/signs-symptoms/melanoma-signs-and-symptoms
http://www.cancer.gov/cancertopics/pdq/genetics/skin/HealthProfessional/page4#Section_165
http://en.wikipedia.org/wiki/File:Protein_CDKN2A_PDB_1a5e.png
Bishop, DT et al. (2009). Genome-wide association study identifies three loci associated with melanoma risk. Nature Genetics, 41(8), 920-5.
doi: 10.1038/ng.411.
Cabanillas, Rubén et al. (2011). Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas. Head and Neck. doi: 10.1002/hed.21911
Lesueur, F et al. (2008). The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. British Journal of Cancer. 99(2), 364-70. doi: 10.1038/sj.bjc.6604470
Miller, A et al. (2006). Melanoma. The New England Journal of Medicine. 355(1), 51-65. PMID:16822996
Nikolaou, V et al. (2011). Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. British Journal of Dermatology, 165(6), 1219-22. doi: 10.1111/j.1365-2133.2011.10551.x
Reginster, M et al. (2011). Molecular Dermapathology in Malignant Melanoma. Dermatology Research and Practice. 2012(684032). doi:10.1155/2012/684032
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001853/
http://www.aad.org/skin-conditions/dermatology-a-to-z/melanoma/signs-symptoms/melanoma-signs-and-symptoms
http://www.cancer.gov/cancertopics/pdq/genetics/skin/HealthProfessional/page4#Section_165
http://en.wikipedia.org/wiki/File:Protein_CDKN2A_PDB_1a5e.png