Melanoma

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.

Cancer

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]

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.

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)
Cobimetinib fumarate [DR:D10615] (BRAF mutation positive)
Hydroxyurea [DR:D00341]
Talimogene laherparepvec [DR:D09966]
Interferon alfa-2b [DR:D02745]
Peginterferon alfa-2b [DR:D02748]
Aldesleukin [DR:D00748]

ICD-O: 8720/3, Tumor type: Malignant melanoma

PMID:16822996 (gene, tumor type)

Miller AJ, Mihm MC Jr.

Melanoma.

N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166

PMID:15468170 (gene)

Tsai KY, Tsao H.

The genetics of skin cancer.

Am J Med Genet C Semin Med Genet 131C:82-92 (2004)
DOI:10.1002/ajmg.c.30037

PMID:15785879 (gene)

Gray-Schopfer VC, da Rocha Dias S, Marais R.

The role of B-RAF in melanoma.

Cancer Metastasis Rev 24:165-83 (2005)
DOI:10.1007/s10555-005-5865-1

PMID:9091799 (carcinogen)

Stern RS, Nichols KT, Vakeva LH.

Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study.

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DOI:10.1056/NEJM199704103361501

PMID:15701081 (carcinogen)

Hussein MR.

Ultraviolet radiation and skin cancer: molecular mechanisms.

J Cutan Pathol 32:191-205 (2005)
DOI:10.1111/j.0303-6987.2005.00281.x

PMID:14643412 (carcinogen)

Rossman TG.

Mechanism of arsenic carcinogenesis: an integrated approach.

Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009

PMID:15660110 (carcinogen)

Luch A.

Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546

PMID:17530489 (carcinogen)

Abnet CC.

Carcinogenic food contaminants.

Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733

PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)

PMID:9498901 (carcinogen)

Tolbert PE.

Oils and cancer.

Cancer Causes Control 8:386-405 (1997)

(drug)

Papadakis MA and McPhee SJ |(ed)

Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition

McGraw Hill Education