Malignant metamorphosis: developmental genes as culprits for oncogenesis in Xiphophorus

Neoplastic growth is a widespread developmental aberration among multicellular organisms ranging from primitive avertebrates such as coelenterates (Brien, 1961) and annelids (Cooper, 1969) to man. A major goal of the studies concerning neoplasia has been to obtain insight into its cellular and molecular basis, and it has been suggested as early as the beginning of this century that cellular genes are paramount in the etiology of neoplasis. Early support for this idea has been gained by Mendelian strategies applied to a number of experimental systems, such as Xiphophorus. During the last years molecular biology has provided some insight into the genetic mechanisms that might be involved in neoplasia in higher vertebrates, and it has been possible to identify proto-oncogenes as candidates for the agents directing cellular transformation and/or maintainance of the neoplastic state of the cell. The high degree of evolutionary conservation of the proto-oncogenes points to basic functions that these genes normally might have for the cell and at the same time indicates that crucial steps associated with tumorigenesis might take similar pathways in different classes of vertebrates. There are now four main lines of molecular evidence that relate cellular genes to neoplasia: insertional mutagenesis or chromosomal rearrangement that juxtaposes an exogenous or endogenous genetic element which augments gene expression next to a cellular gene, resulting in elevated expression (for review, see Varmus, 1982; Klein, 1983); gene amplification that results in an increase of the copy number and an elevated expression of a particular gene and, to date, has been found in tumors of humans and mice (for overviews, see Schwab et al., 1984; Schwab, 1985; Alitalo and Schwab, 1986); structural alteration of a cellular gene itself which results in the synthesis of an altered protein (Weinberg, 1982; Cooper, 1982); and generation of fusion genes as a result of gene translocation with possibly altered biological activities (for review, see Adams, 1985). It remains to be addressed in future experiments which genetic mechanisms are operative in development of tumors of genetic origin in Xiphophorus.