Nonrandom chromosome losses in stepwise neoplastic transformation in vitro of human uroepithelial cells

An in vitro/in vivo transformation system was used to study chromosome region losses in stepwise neoplastic transformation and progression of human uroepithelial cells. Complete cytogenetic analyses were done on 17 independent carcinomas derived using this system and showed that losses of chromosome regions on 3p (P = 0.0003), 6q (P = 0.01), and 18q (P = 0.0003) were nonrandom. The smallest common losses [i.e., 3(p13----pter), 6(q21----q23), and 18(q21.1----qter)] were in putative cancer suppressor gene regions. In addition, cumulative losses from a group of 10 chromosome arms (i.e., 1p, 1q, 3p, 5q, 6q, 9q, 11p, 13q, 17p, and 18q) frequently deleted in clinical carcinomas were very significant (P = 0.0005) compared to losses from all other arms. Loss of 3p and 18q both correlated with transformation to high grade carcinomas (P = 0.001 and P = 0.004, respectively). These data provide new evidence supporting hypotheses that chromosome regions 3(p13----pter) and 6(q21----q23) contain genes that suppress cancer development. These results also provide new data confirming the hypothesis that genetic loss(es) in the 18(q21.1----qter) region are associated with the development of high grade malignancies.