Nonrandom chromosome losses in tumorigenic revertants of hybrids between isogeneic immortal and neoplastic human uroepithelial cells.

Somatic cell hybrid analysis was used to examine the role of recessive cancer genes in tumorigenic transformation in vitro of human uroepithelial cells (HUC). Hybrids between nontumorigenic pseudodiploid SV40-immortalized HUC (SV-HUC) and two aggressive grade III transitional cell carcinomas (TCC) produced in nude mice after in vitro exposure of SV-HUC to 3-methylcholanthrene (MC) were completely suppressed for tumorigenicity at early passage. Tumorigenic reversion occurred after five or more passages in culture and was always accompanied by chromosome losses. Overall, the tumorigenic revertants showed statistically significant losses of chromosomes 1, 4, 5, 9q, 12, 14q, and 17 (all P less than or equal to 0.05) as compared to losses in suppressed hybrids. In addition, hybrid reversion was accompanied by losses that left specific tumors with a single remaining homolog of certain chromosomes (i.e., 3, 5q, 11p, 17p, and 18q). These losses were also considered significant because of the likelihood that genes on these chromosomes were reduced to homozygosity. Many of the significant losses (i.e., 5q, 9q, 11p, and 17p) were of chromosomes that are frequently lost in clinical TCC. Thus, these results support the hypothesis that these chromosomes contain genes whose loss leads to HUC tumorigenesis.