The Role of Oncogenes in the Pathogenesis of Malignant Melanoma

Abstract

The title of this chapter, ‘The Role of Oncogenes in the Pathogenesis of Malignant Melanoma,’ intimates knowledge of a specific action of an oncogene(s) which is directly involved in the development of melanoma; none is yet known. As of this writing, the genetic changes that lead to malignant transformation in this disease are unknown. Moreover, there is, as yet, no direct evidence that the action of any oncogene is responsible for the initiation or maintenance of any human cancer. Yet it is a widely held belief that such evidence is not only forthcoming, but the outlines of this evidence are already discernible. Current dogma maintains that proto-oncogenes, the normal unmodified gene counterparts of oncogenes, play complex but fundamental roles in the control of normal cellular growth and in other functions unrelated to proliferation. The evidence for this is multifaceted and has been extensively reported. Oncogenes, being permuted variants of proto-oncogenes, are involved, therefore, in perturbing the normal mechanisms in which these genes are involved, with the end result being neoplasia. In this chapter we will discuss the relatively limited amount of available information on the status of both proto-oncogenes and oncogenes in malignant melanoma and in premalignant and normal prescursor tissues. Further, we will discuss the interrelatedness of melanocyte-melanoma cellular differentiation programs and the process of malignant transformation.