Melanoma causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Overview

Melanoma may be caused by sporadic genetic (e.g. BRAF and/or N-RAS) or may be part of familial syndromes (e.g. familial atypical multiple mole melanoma syndrome).

Causes

Malignant melanoma arises from the epidermal melanocytes, which are neural crest cells involved in the synthesis of melanin (a brown pigment with photoprotective properties). Melanoma may be caused by sporadic genetic mutations (e.g. BRAF and/or N-RAS) or may be part of familial syndromes.

Sporadic Melanoma

• The majority of cases of melanoma are due to sporadic genetic mutations (90%).
• More than one genetic mutation is usually required for the development of melanoma (multiple hits).
• The most common mutations that result in the development of melanoma are BRAF (approximately 50% of melanomas) and N-RAS (approximately 15% of melanomas).

Familial Melanoma

Melanoma may be caused by hereditary diseases (10%) and is associated with mutations of the P16/CDKN2A gene:

• Familial atypical multiple mole melanoma syndrome (FAMMM syndrome)
• Melanoma-astrocytoma syndrome