[Frontiers in Bioscience 3, d1005-1010, September 15, 1998] |
MOLECULAR EVENTS IN MELANOMA DEVELOPMENT AND PROGRESSION
Friedegund Meier1, Kapaettu Satyamoorthy1, Mark Nesbit1, Mei-Yu Hsu1, Birgit Schittek2, Claus Garbe2, and Meenhard Herlyn1
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 191041, Department of Dermatology, University of Tuebingen, Liebermeisterstr.25, 72076 Tuebingen, Germany2
Received 7/17/98 Accepted 8/10/98
Based on clinical and histopathological features, five steps of melanoma progression have been proposed: common acquired and congenital nevi with structurally normal melanocytes, dysplastic nevus with structural and architectural atypia, early radial growth phase (RGP) primary melanoma, advanced vertical growth phase primary melanoma (VGP) with competence for metastasis, and metastatic melanoma. Despite a wealth of research resources (tissues, cell lines, and antibodies), the genetic alterations responsible for the development and stepwise progression of melanoma are still unclear. Cytogenetic analyses have failed to identify consistent gene deletions, mutations, translocations, or amplifications in sporadic cases. However, in vitro characterization of melanoma cells has revealed fundamental differences from normal melanocytes. Earlier work using monoclonal antibodies has defined a variety of melanoma-associated antigens that mediate cell-cell or cell-substratum adhesion, growth regulation, proteolysis, and modulation of immune responses. Functional studies of these individual candidate molecules will lead to a better understanding of the pathogenesis of melanoma and of potential targets for rational therapy.