Loss of 3p13----p21.2 in tumorigenic reversion of a hybrid between isogeneic nontumorigenic and tumorigenic human uroepithelial cells.
Previous studies in our laboratory showed nonrandom losses of chromosome 3p in association with tumorigenic transformation of SV40-immortalized human uroepithelial cells (HUC) to high grade cancers. To test the hypothesis that genes on 3p suppress HUC tumorigenesis, somatic cell hybrids were formed between nontumorigenic SV40-immortalized HUC and an isogeneic derivative transitional cell carcinoma line, MC-T16, that lost 3p on initial transformation. All hybrids were initially tumorigenically suppressed and reversion was always associated with genetic losses, including losses of 3p (Klingelhutz et al., Somatic Cell Mol. Genet., 17: 551-565, 1991). In this paper, we report that the smallest 3p region lost in a tumorigenic hybrid revertant (THR-X) in this system was an unusual interstitial deletion of 3p13----p21.2. Restriction fragment length polymorphism analysis confirmed this loss by showing that THR-X was reduced to homozygosity for D3S30, a 3p13 probe, but remained heterozygous for the distal 3p21.3 probe, D3F15S2. These data, along with our previous report identifying loss of 3p13----p14.2 as the smallest 3p region deleted in association with SV40-immortalized HUC tumorigenic transformation (Klingelhutz et al., Genes Chromosomes Cancer, 3: 346-357, 1991), provide compelling new evidence for a bladder cancer suppressor gene in the 3p13----p21.2 region.
Klingelhutz
A J
AJ
Department of Human Oncology, University of Wisconsin, Madison 53792.
Wu
S Q
SQ
Huang
J
J
Reznikoff
C A
CA
D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002461:Cell Line, Transformed; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D016153:Genes, Suppressor; D006579:Heterozygote; D006801:Humans; D006822:Hybrid Cells; D013539:Simian virus 40; D001749:Urinary Bladder Neoplasms / Q000235:genetics*