Molecular and genetic mechanisms in melanoma.
Recent studies have indicated an increasing incidence of melanoma worldwide. Although UV signature mutations are found rarely in melanoma cells, there is some evidence that intense intermittent exposure to sunlight can induce melanocyte tumorigenesis, and this is also observed after UV irradiation in some animals. The purpose of this paper is to review some of the most important mechanisms involved in the pathogenesis of this tumor. Genetic studies showed the familiar melanoma is linked to the mutation or deletion of the suppressor gene CDKN2A, and perhaps to CDK4. Studies showed that BRAF mutation is frequent in primary and metastatic melanoma cells but also in naevocytic nevi. This mutation activates the RAF/MEK pathway. Exposure to UV radiation induces immunosuppression. Recent investigations showed that chemokines, angiogenesis, metalloproteinases can play a role in the mechanism of metastasis. In spite of these advances the initiating events are still not completely understood. In conclusion, the pathogenesis of melanoma is very complex because numerous genetic and epigenetic factors are implicated in its development and progression, but some of the showed mechanisms can be targets for new therapies.
Gruber
Franjo
F
Department of Dermatovenerology, University Hospital Centre Rijeka, Rijeka, Croatia. franjo.gruber@ri.t-com.hr
Kastelan
Marija
M
Brajac
Ines
I
Saftić
Marina
M
Peharda
Vesna
V
Cabrijan
Leo
L
Stanić Zgombić
Zrinka
Z
Simonić
Edita
E
D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D019942:Genes, p16; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects; D008545:Melanoma / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D019098:Telomerase / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
D019098:Telomerase