[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
4. GENETIC BASIS OF MELANOMA
The genetic changes that lead to melanoma are still poorly understood. Table 2 summarizes the current information on specific gene deletions, mutations, translocations, or overexpression. Less is known about the genetic abnormalities in melanoma than in other cancers such as leukemias, lymphomas, or gliomas and various carcinomas. Unlike many other cancers, melanomas show very few mutations in the p53 tumor suppressor gene. Mutations and deletions in p16 are also less frequent in sporadic melanoma than in other types of cancers such as pancreatic carcinoma (12). Similarly, n-ras mutations are relatively rare and are more frequently seen in sun-exposed areas of the skin. Stabilization of beta-catenin due to mutations has only recently been described in melanoma (16). Since beta-catenin mutations lead to gene activation through complex formation with Lef/Tcf transcription factors (17), it is possible that constitutive expression of this signaling molecule plays a role in melanomagenesis. Although the downstream effectors of the Lef/Tcf pathway are presently unknown, melanoma cells display a variety of antigens (melanoma-associated antigens) that are generally not found on normal melanocytes. These molecules are associated with survival, growth, motility, adhesion, invasion, and inflammatory and immune responses (figure 3), many of which have been defined with monoclonal antibodies (MAbs) that are now extensively used for diagnosis and even therapy.
Figure 3. Antigens on melanoma cells. MAbs have defined a variety of structures on melanoma cells that have functional significance for growth, adhesion, transport, invasion, and interactions with the microenvironment. The patterns of antigen expression of melanoma cells are very different from those in melanocytes. Melanoma cells, but not melanocytes, display melanoma-associated antigens that may be shared by monocytes, fibroblasts, or endothelial cells.
Table 2. Molecular abnormalities in sporadic melanoma