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.


Malignant melanoma arises from the epidermal melanocytes, which are neural crest cells involved in the synthesis of melanin (a brown pigment with photo-protective properties). 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).


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.[1]

Sporadic Melanoma

Familial Melanoma

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


  1. 1.0 1.1 O'Brien O, Lyons T, Murphy S, Feeley L, Power D, Heffron C (November 2017). "BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing methods". J. Clin. Pathol. 70 (11): 935–940. doi:10.1136/jclinpath-2017-204367. PMID 28424234. Vancouver style error: initials (help)
  2. Wong K, Robles-Espinoza CD, Rodriguez D, Rudat SS, Puig S, Potrony M, Wong CC, Hewinson J, Aguilera P, Puig-Butille JA, Bressac-de Paillerets B, Zattara H, van der Weyden L, Fletcher C, Brenn T, Arends MJ, Quesada V, Newton-Bishop JA, Lopez-Otin C, Bishop DT, Harms PW, Johnson TM, Durham AB, Lombard DB, Adams DJ (December 2018). "Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma". JAMA Dermatol. doi:10.1001/jamadermatol.2018.3662. PMID 30586141. Vancouver style error: initials (help)
  3. Ponti G, Manfredini M, Greco S, Pellacani G, Depenni R, Tomasi A, Maccaferri M, Cascinu S (December 2017). "BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival". Anticancer Res. 37 (12): 7043–7048. doi:10.21873/anticanres.12175. PMID 29187493.
  4. Parekh V, Sobanko J, Miller CJ, Karakousis G, Xu W, Letrero R, Elenitsas R, Xu X, Elder DE, Amaravadi R, Schuchter LM, Nathanson KL, Wilson MA, Chu EY (December 2018). "NRAS Q61R and BRAF G466A mutations in atypical melanocytic lesions newly arising in advanced melanoma patients treated with vemurafenib". J. Cutan. Pathol. doi:10.1111/cup.13401. PMID 30552700.
  5. Perkins A, Duffy RL (June 2015). "Atypical moles: diagnosis and management". Am Fam Physician. 91 (11): 762–7. PMID 26034853.
  6. Cremin C, Howard S, Le L, Karsan A, Schaeffer DF, Renouf D, Schrader KA (2018). "CDKN2A founder mutation in pancreatic ductal adenocarcinoma patients without cutaneous features of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome". Hered Cancer Clin Pract. 16: 7. doi:10.1186/s13053-018-0088-y. PMC 5842519. PMID 29541281.
  7. Chan AK, Han SJ, Choy W, Beleford D, Aghi MK, Berger MS, Shieh JT, Bollen AW, Perry A, Phillips JJ, Butowski N, Solomon DA (2017). "Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history". Clin. Neuropathol. 36 (5): 213–221. doi:10.5414/NP301022. PMC 5628627. PMID 28699883.