TUMOR-SUPPRESSOR GENES STUDIED BY CELL HYBRIDIZATION AND CHROMOSOME TRANSFER

Although the cloning of tumor suppressor genes has proved to be an ard uous task, often involving several years of labor intensive cloning st rategies, a greater understanding of neoplastic progression will be ma de once the function and role of these genes have been sorted out. To fully appreciate the state at which this field of research currently i s, however, one must understand that the road to tumor suppression was paved by both somatic cell hybridization and chromosome transfer stud ies. Although regarded by many as laboratory artifact, somatic cell hy bridization has provided strong circumstantial evidence, if not formal proof, for the existence of tumor suppressor genes. In further reduci ng the complexity associated with whole genome transfer, single chromo some transfer was subsequently developed as a refinement to this techn ique so that one could unequivocally correlate suppression with a part icular chromosome. We have learned from these studies that single chro mosomes harbor the genetic information necessary to reverse the malign ant phenotype associated with cancer cells. Furthermore, multiple tumo r suppressor loci are now known to exist, with one to several differen t loci associated with a given tumor type. In this review, we present evidence for tumor suppressor genes and discuss the early studies that led to their discovery.