KEGG   DISEASE: MelanomaHelp
Entry
H00038                      Disease                                

Name
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
Human diseases [BR:br08402]
 Cancers
  Skin cancers
   H00038  Melanoma
Human diseases in ICD-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C43-C44  Melanoma and other malignant neoplasms of skin
   C43  Malignant melanoma of skin
    H00038  Melanoma
Tumor markers [br08442.html]
 H00038
Cancer-accociated carbohydrates [br08441.html]
 H00038
BRITE hierarchy
Pathway
Melanoma
Network
N00012  
Mutation-activated KRAS/NRAS to ERK signaling pathway
N00013  
Mutation-activated BRAF to ERK signaling pathway
N00032  
Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00051  
Deleted PTEN to PI3K signaling pathway
N00052  
Mutation-inactivated PTEN to PI3K signaling pathway
N00067  
Deleted p14(ARF) to p21-cell cycle G1/S
N00070  
Mutation-inactivated p16(INK4a) to p16-cell cycle G1/S
N00071  
Deleted p16(INK4a) to p16-cell cycle G1/S
N00073  
Mutation-activated CDK4 to cell cycle G1/S
N00076  
Mutation-inactivated p14(ARF) to p21-cell cycle G1/S
N00115  
Mutation-inactivated TP53 to transcription
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.
Drug
Dacarbazine [DR:D00288]
Ipilimumab [DR:D04603]
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574]
Vemurafenib [DR:D09996] (BRAF mutation positive)
Dabrafenib mesylate [DR:D10104] (BRAF mutation positive)
Trametinib dimethyl sulfoxide [DR:D10176] (BRAF mutation positive)
Hydroxyurea [DR:D00341]
Interferon alfa-2b [DR:D02745]
Peginterferon alfa-2b [DR:D02748]
Aldesleukin [DR:D00748]
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)
DOI:10.1056/NEJMra052166
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)
DOI:10.1002/ajmg.c.30037
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)
DOI:10.1007/s10555-005-5865-1
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)
DOI:10.1056/NEJM199704103361501
Reference
PMID:15701081 (carcinogen)
  Authors
Hussein MR.
  Title
Ultraviolet radiation and skin cancer: molecular mechanisms.
  Journal
J Cutan Pathol 32:191-205 (2005)
DOI:10.1111/j.0303-6987.2005.00281.x
Reference
PMID:14643412 (carcinogen)
  Authors
Rossman TG.
  Title
Mechanism of arsenic carcinogenesis: an integrated approach.
  Journal
Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
Reference
PMID:17530489 (carcinogen)
  Authors
Abnet CC.
  Title
Carcinogenic food contaminants.
  Journal
Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733
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
Papadakis MA and McPhee SJ |(ed)
  Title
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
  Journal
McGraw Hill Education
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