KEGG   DISEASE: Melanoma
Entry
H00038                      Disease                                
Name
Melanoma
  Subgroup
Cutaneous malignant melanoma (CMM)
  Supergrp
Solid tumor [DS:H02421]
Description
Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression.
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Skin cancers
   H00038  Melanoma
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of skin
     2C30  Melanoma of skin
      H00038  Melanoma
Tumor markers [br08442.html]
 H00038
Cancer-associated carbohydrates [br08441.html]
 H00038
Pathway
hsa05218  Melanoma
Related
pathway
hsa05200  Pathways in cancer
hsa05225  Hepatocellular carcinoma
Network
nt06268  Melanoma
Gene
(CMM2) CDKN2A [HSA:1029] [KO:K06621]
(CMM3) CDK4 [HSA:1019] [KO:K02089]
(CMM5) MC1R [HSA:4157] [KO:K04199]
(CMM6) XRCC3 [HSA:7517] [KO:K10880]
(CMM8) MITF (amplification) [HSA:4286] [KO:K09455]
(CMM9) TERT [HSA:7015] [KO:K11126]
(CMM10) POT1 [HSA:25913] [KO:K11109]
BRAF [HSA:673] [KO:K04365]
STK11 [HSA:6794] [KO:K07298]
NRAS [HSA:4893] [KO:K07828]
PTEN [HSA:5728] [KO:K01110]
TP53 [HSA:7157] [KO:K04451]
Carcinogen
8-Methoxypsoralen (Methoxsalen) plus ultraviolet A radiation [CPD:C01864]
Solar radiation
*Benzo[a]pyrene [CPD:C07535]
*Chimney sweeping
*Mineral oils, untreated and mildly treated
*: Although this is a risk factor for skin cancer in general, the strength of association with different histological tumor types is not well understood.
Drug
Dacarbazine [DR:D00288]
Vemurafenib [DR:D09996] (BRAF mutation positive)
Dabrafenib mesylate [DR:D10104] (BRAF mutation positive)
Encorafenib [DR:D11053] (BRAF mutation positive)
Trametinib dimethyl sulfoxide [DR:D10176] (BRAF mutation positive)
Cobimetinib fumarate [DR:D10615] (BRAF mutation positive)
Binimetinib [DR:D10604] (BRAF mutation positive)
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574]
Ipilimumab [DR:D04603]
Talimogene laherparepvec [DR:D09966]
Interferon alfa-2b [DR:D02745]
Peginterferon alfa-2b [DR:D02748]
Aldesleukin [DR:D00748]
Tebentafusp [DR:D12296] (HLA-A*02:01-positive)
Nivolumab and relatlimab [DR:D12334]
Other DBs
ICD-11: 2C30
ICD-10: C43
MeSH: D008545
OMIM: 613099 613972 615134 155600 155601 609048 614456 615848
Reference
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
  Authors
Tsai KY, Tsao H.
  Title
The genetics of skin cancer.
  Journal
Am J Med Genet C Semin Med Genet 131C:82-92 (2004)
DOI:10.1002/ajmg.c.30037
Reference
PMID:17492760 (CDKN2A)
  Authors
Kannengiesser C, Dalle S, Leccia MT, Avril MF, Bonadona V, Chompret A, Lasset C, Leroux D, Thomas L, Lesueur F, Lenoir G, Sarasin A, Bressac-de Paillerets B
  Title
New founder germline mutations of CDKN2A in melanoma-prone families and multiple primary melanoma development in a patient receiving levodopa treatment.
  Journal
Genes Chromosomes Cancer 46:751-60 (2007)
DOI:10.1002/gcc.20461
Reference
PMID:15880589 (CDK4)
  Authors
Molven A, Grimstvedt MB, Steine SJ, Harland M, Avril MF, Hayward NK, Akslen LA
  Title
A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation.
  Journal
Genes Chromosomes Cancer 44:10-8 (2005)
DOI:10.1002/gcc.20202
Reference
PMID:16809487 (MC1R)
  Authors
Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, Calista D, Kanetsky PA, Pinkel D, Bastian BC
  Title
MC1R germline variants confer risk for BRAF-mutant melanoma.
  Journal
Science 313:521-2 (2006)
DOI:10.1126/science.1127515
Reference
PMID:11059748 (XRCC3)
  Authors
Winsey SL, Haldar NA, Marsh HP, Bunce M, Marshall SE, Harris AL, Wojnarowska F, Welsh KI
  Title
A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer.
  Journal
Cancer Res 60:5612-6 (2000)
Reference
PMID:22012259 (MITF)
  Authors
Bertolotto C, Lesueur F, Giuliano S, Strub T, de Lichy M, Bille K, Dessen P, d'Hayer B, Mohamdi H, Remenieras A, Maubec E, de la Fouchardiere A, Molinie V, Vabres P, Dalle S, Poulalhon N, Martin-Denavit T, Thomas L, Andry-Benzaquen P, Dupin N, Boitier F, Rossi A, Perrot JL, Labeille B, Robert C, Escudier B, Caron O, Brugieres L, Saule S, Gardie B, Gad S, Richard S, Couturier J, Teh BT, Ghiorzo P, Pastorino L, Puig S, Badenas C, Olsson H, Ingvar C, Rouleau E, Lidereau R, Bahadoran P, Vielh P, Corda E, Blanche H, Zelenika D, Galan P, Aubin F, Bachollet B, Becuwe C, Berthet P, Bignon YJ, Bonadona V, Bonafe JL, Bonnet-Dupeyron MN, Cambazard F, Chevrant-Breton J, Coupier I, Dalac S, Demange L, d'Incan M, Dugast C, Faivre L, Vincent-Fetita L, Gauthier-Villars M, Gilbert B, Grange F, Grob JJ, Humbert P, Janin N, Joly P, Kerob D, Lasset C, Leroux D, Levang J, Limacher JM, Livideanu C, Longy M, Lortholary A, Stoppa-Lyonnet D, Mansard S, Mansuy L, Marrou K, Mateus C, Maugard C, Meyer N, Nogues C, Souteyrand P, Venat-Bouvet L, Zattara H, Chaudru V, Lenoir GM, Lathrop M, Davidson I, Avril MF, Demenais F, Ballotti R, Bressac-de Paillerets B
  Title
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
  Journal
Nature 480:94-8 (2011)
DOI:10.1038/nature10539
Reference
PMID:23348506 (TERT)
  Authors
Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA
  Title
Highly recurrent TERT promoter mutations in human melanoma.
  Journal
Science 339:957-9 (2013)
DOI:10.1126/science.1229259
Reference
PMID:24686849 (POT1)
  Authors
Robles-Espinoza CD, Harland M, Ramsay AJ, Aoude LG, Quesada V, Ding Z, Pooley KA, Pritchard AL, Tiffen JC, Petljak M, Palmer JM, Symmons J, Johansson P, Stark MS, Gartside MG, Snowden H, Montgomery GW, Martin NG, Liu JZ, Choi J, Makowski M, Brown KM, Dunning AM, Keane TM, Lopez-Otin C, Gruis NA, Hayward NK, Bishop DT, Newton-Bishop JA, Adams DJ
  Title
POT1 loss-of-function variants predispose to familial melanoma.
  Journal
Nat Genet 46:478-481 (2014)
DOI:10.1038/ng.2947
Reference
PMID:15785879 (BRAF)
  Authors
Gray-Schopfer VC, da Rocha Dias S, Marais R.
  Title
The role of B-RAF in melanoma.
  Journal
Cancer Metastasis Rev 24:165-83 (2005)
DOI:10.1007/s10555-005-5865-1
Reference
PMID:10208439 (STK11)
  Authors
Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin AF, Zeuthen J
  Title
Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma.
  Journal
Oncogene 18:1777-80 (1999)
DOI:10.1038/sj.onc.1202486
Reference
PMID:19037234 (NRAS BRAF)
  Authors
Greene VR, Johnson MM, Grimm EA, Ellerhorst JA
  Title
Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma.
  Journal
J Invest Dermatol 129:1483-8 (2009)
DOI:10.1038/jid.2008.374
Reference
PMID:10651986 (PTEN)
  Authors
Birck A, Ahrenkiel V, Zeuthen J, Hou-Jensen K, Guldberg P
  Title
Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies.
  Journal
J Invest Dermatol 114:277-80 (2000)
DOI:10.1046/j.1523-1747.2000.00877.x

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