Abstract
Loss of heterozygosity (LOH) and allelic im- balance (AI) are widely recognized ways of localizing tu- mor suppressor genes. We have demonstrated structural alterations of chromosome 5 in 12 human prostate cancer cell lines. After mapping the breakpoints involved in trans- locations and deletions in chromosome 5, the 5q11 region was found to be the most consistent breakpoint. In this study, we further analyzed the 5q11 region in several prostate can- cer cell lines as well as tumor samples from prostate cancer patients. Five different polymorphic sequence tagged sites (STSs) (D5S430, D5S822, D5S664, D5S645, and D5S2068) from this region were evaluated for LOH in order to dis- cern the specific breakpoint in chromosome 5. A breakpoint was shown between the markers D5S2068 and D5S407 in the PC-3M human prostate cancer cell line. Allelotyping of prostate tumor samples revealed LOH in 6 (65%) of 9 tumor samples in at least one of the markers tested. In addi- tion, in three cell lines (DU-145, MDAPCa2b and C4-2) microsatellite instability (MSI), shown as gain of alleles, was observed, suggesting RER + phenotype. These results implicated 5q11 and specifically the region surrounding markers D5S2068 as a region of interest for locating a tu- mor suppressor gene in human prostate cancer.
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