Entry 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.
Class Human Diseases; Cancer: specific typesBRITE hierarchy
Pathway map Disease Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02158 BAD; Bcl-2-antagonist of cell death
K02159 BAX; apoptosis regulator BAX
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04357 EGF; epidermal growth factor
K04358 FGF; fibroblast growth factor
K04359 PDGFA; platelet-derived growth factor subunit A
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04363 PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1 ]
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04402 GADD45; growth arrest and DNA-damage-inducible protein
K04451 TP53, P53; tumor protein p53
K04503 CCND1; G1/S-specific cyclin-D1
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05089 PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1 ]
K05099 MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1 ]
K05450 PDGFC_D; platelet derived growth factor C/D
K05459 IGF1; insulin-like growth factor 1
K05460 HGF; hepatocyte growth factor
K05689 CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K06618 RB1; retinoblastoma-associated protein
K06620 E2F3; transcription factor E2F3
K06621 CDKN2A, P16, INK4A; cyclin-dependent kinase inhibitor 2A
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07827 KRAS, KRAS2; GTPase KRas
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09389 E2F2; transcription factor E2F2
K09455 MITF; microphthalmia-associated transcription factor
K10140 DDB2; DNA damage-binding protein 2
K14021 BAK, BAK1; Bcl-2 homologous antagonist/killer
K17386 PDGFB; platelet-derived growth factor subunit B
K17454 E2F1; transcription factor E2F1
K18496 FGF1; fibroblast growth factor 1
K18497 FGF2; fibroblast growth factor 2
K22428 FGF23; fibroblast growth factor 23
K22429 FGF21; fibroblast growth factor 21
K22603 FGF19; fibroblast growth factor 19
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Miller AJ, Mihm MC Jr.
Title Melanoma.
Journal Reference Authors Chin L.
Title The genetics of malignant melanoma: lessons from mouse and man.
Journal Reference Authors Takata M, Saida T.
Title Genetic alterations in melanocytic tumors.
Journal Reference Authors Chudnovsky Y, Khavari PA, Adams AE.
Title Melanoma genetics and the development of rational therapeutics.
Journal Reference Authors Merlino G.
Title Cancer biology: the weakest link?
Journal Reference Authors Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR.
Title Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.
Journal Reference Authors Levy C, Khaled M, Fisher DE.
Title MITF: master regulator of melanocyte development and melanoma oncogene.
Journal Reference Authors Tsao H, Goel V, Wu H, Yang G, Haluska FG.
Title Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma.
Journal Reference Authors Gruss C, Herlyn M.
Title Role of cadherins and matrixins in melanoma.
Journal Reference Authors Thompson JF, Scolyer RA, Kefford RF.
Title Cutaneous melanoma.
Journal Reference Authors Omholt K, Platz A, Kanter L, Ringborg U, Hansson J.
Title NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.
Journal Clin Cancer Res 9:6483-8 (2003)
Reference Authors Hussein MR.
Title The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship?
Journal Reference Authors Lazar-Molnar E, Hegyesi H, Toth S, Falus A.
Title Autocrine and paracrine regulation by cytokines and growth factors in melanoma.
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