MINIMAL DELETION OF 3P13-]14.2 ASSOCIATED WITH IMMORTALIZATION OF HUMAN UROEPITHELIAL CELLS

Immortalization and tumorigenic transformation of many human cell type s, including human uroepithelial cells (HUCs), are frequently associat ed with loss of genetic material from the short arm of chromosome 3 (3 p). In addition, losses of 3p have been observed in many human cancers including renal cell carcinoma, lung cancer, breast cancer, and bladd er cancer. Genetic studies suggest that there are at least two regions on 3p in which tumor suppressor genes might be located, but the preci se location of these genes is not known. We studied chromosome 3 losse s that were specifically associated with immortalization of five indep endent human papilloma virus 16 (HPV16) Eb-or E7-transformed HUCs. Cyt ogenetic analysis showed that the smallest common region of deletion w as 3p14.1-->14.2. Fluorescence in situ hybridization using a 3p13-->14 -specific yeast artificial chromosome (YAC) contig showed the precise localization of the breakpoints to be in 3p13 and 3p14.2, thus definin g the smallest common overlap of 3p deletions in HPV16 E6- or E7-immor talized HUCs. These results suggest the presence in this region of gen es involved in the control of senescence in vitro and possibly tumorig enesis in vivo.