Molecular genetics of human malignant melanoma

Publisher Website
Google Scholar
Abstract
The idea that cancer is a genetic disease is over 80 years old [1]; that cancer is also a progressive genetic disease is a more recent, but fundamentally critical, expansion of this idea [2]. Due to increasingly sensitive techniques and novel methodological advancements, the supposition that tumors form because of a progressive development in the number and types of genetic defects is being confirmed at the molecular level [3]. Molecular geneticists are now faced with two formidable tasks. The first is to decipher the precise nature and sequence of genetic perturbations that characterize the malignant process at each of its progressive stages. The second is to define the biochemical and biological impact of these genetic events on the interdependent mechanisms that govern the proliferation, differentiation, and intercellular relationships of the normal cell. In this regard, human malignant melanoma provides a particularly good model for studying progressive etiologically relevant events, since clinical and pathological observations have defined cutaneous lesions that represent sequential steps in the progression to melanoma [4–6]. Moreover, cells representing these stages (e.g., normal melanocytes, dysplastic nevi, primary and metastatic melanomas) can be cultured in sufficient quantities to permit a wide range of experiments, including the development of in vitro models of transformation. Consistent abnormalities in chromosomes 1, 6, 7, and 9, as well as alterations in antigen expression, biological characteristics, differentiation programs, growth factor requirements, and proto-oncogene expression and extinction, have been observed to accompany tumor progression of the melanocyte [7–10].