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Pathology Research International
Volume 2011 (2011), Article ID 159421, 8 pages
http://dx.doi.org/10.4061/2011/159421
Review Article

Molecular Bases of Cutaneous and Uveal Melanomas

1Department of Pathology and Cell Biology, University of South Florida College of Medicine, 12901 Bruce B. Downs Boulevard, MDC 11, Tampa, FL 33612, USA
2Department of Pathology, H. Lee Moffitt Cancer Center, 2nd Floor, 12902 Magnolia Dr., Tampa, FL 33612, USA

Received 15 March 2011; Revised 27 May 2011; Accepted 30 May 2011

Academic Editor: Gerardo Ferrara

Copyright © 2011 Sudeep Gaudi and Jane L. Messina. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.