[Tumor-suppressor genes].

The existence of tumor-suppressor genes has been primarily suggested by three lines of evidences: 1) the suppression of transformed phenotypes of tumor cells by cell-cell hybridization with normal cells; 2) non-random chromosome deletions in a variety of tumors; 3) loss of heterozygosity in specific chromosomal regions in tumor cells. Results from monochromosome transfer experiments also suggest the existence of multiple, functionally distinct tumor-suppressor genes. Recently, several tumor-suppressor genes, which appeared to be functionally distinct, (i.e., Rb gene, WT gene and DCC gene) were isolated. Most recently, it was suggested that the inactivations of at least three different tumor-suppressor genes were required for the colorectal carcinogenesis at different steps. Thus, these findings support that losses or alterations in the dosage of multiple tumor-suppressor genes play crucial roles during initiation and/or progression of a wide variety of cancers.