KEGG   DISEASE: H00038Help
Entry
H00038                      Disease                                

Name
Malignant melanoma
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 hierarchy
Pathway
Melanoma
Gene
BRAF (mutation) [HSA:673] [KO:K04365]
NRAS (mutation) [HSA:4893] [KO:K07828]
CDK4 (mutation) [HSA:1019] [KO:K02089]
MITF (amplification) [HSA:4286] [KO:K09455]
PTEN (deletion, germline mutation, somatic mutation, LOH) [HSA:5728] [KO:K01110]
p16/INK4A (loss/mutation) [HSA:1029] [KO:K06621]
p53 (loss/mutation) [HSA:7157] [KO:K04451]
Carcinogen
8-Methoxypsoralen (Methoxsalen) plus ultraviolet A radiation [CPD:C01864] [DR:D00139]
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.
Marker
Vimentin [HSA:7431]
S100 [HSA:6271]
HMB-45
Mart-1/Melan-A [HSA:2315]
Tyrosinase [HSA:7299]
TyrP1 [HSA:7306]
TyrP2 [HSA:1638]
MITF [HSA:4286]
Drug
Dacarbazine [DR:D00288]
Interferon alpha [DR:D00745 D02745 D03305 D04552 D04553]
Interleukin-2
Comment
ICD-O: 8720/3, Tumor type: Malignant melanoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:16822996 (gene, tumor type)
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
Reference
PMID:15468170 (gene)
  Authors
Tsai KY, Tsao H.
  Title
The genetics of skin cancer.
  Journal
Am J Med Genet C Semin Med Genet 131C:82-92 (2004)
Reference
PMID:15785879 (gene)
  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)
Reference
PMID:15858465 (marker)
  Authors
Carlson JA, Ross JS, Slominski A, Linette G, Mysliborski J, Hill J, Mihm M Jr.
  Title
Molecular diagnostics in melanoma.
  Journal
J Am Acad Dermatol 52:743-75; quiz 775-8 (2005)
Reference
PMID:17439838 (marker)
  Authors
Nonaka D, Laser J, Tucker R, Melamed J.
  Title
Immunohistochemical evaluation of necrotic malignant melanomas.
  Journal
Am J Clin Pathol 127:787-91 (2007)
Reference
PMID:9091799 (carcinogen)
  Authors
Stern RS, Nichols KT, Vakeva LH.
  Title
Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study.
  Journal
N Engl J Med 336:1041-5 (1997)
Reference
PMID:15701081 (carcinogen)
  Authors
Hussein MR.
  Title
Ultraviolet radiation and skin cancer: molecular mechanisms.
  Journal
J Cutan Pathol 32:191-205 (2005)
Reference
PMID:14643412 (carcinogen)
  Authors
Rossman TG.
  Title
Mechanism of arsenic carcinogenesis: an integrated approach.
  Journal
Mutat Res 533:37-65 (2003)
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
Reference
PMID:17530489 (carcinogen)
  Authors
Abnet CC.
  Title
Carcinogenic food contaminants.
  Journal
Cancer Invest 25:189-96 (2007)
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
Reference
PMID:9498901 (carcinogen)
  Authors
Tolbert PE.
  Title
Oils and cancer.
  Journal
Cancer Causes Control 8:386-405 (1997)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

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