P53 GENE ALTERATIONS IN HUMAN PROSTATE CARCINOMA

Alterations of the p53 gene are among the most frequent genetic lesion s in a variety of human malignancies. Their role in prostate cancer is , however, unclear. We have analyzed 10 primary and two metastatic hum an prostate carcinomas as well as 3 prostate cancer cell lines for mut ations of the p53-gene. Using single strand conformational polymorphis m analysis (SSCP) and direct sequencing of the polymerase chain reacti on (PCR) products, p53 mutations were detected in 1 of 10 primary pros tate cancers. By contrast, 1 of 2 metastatic tumors and all 3 prostate cancer cell lines (derived from metastases) were found to contain a m utant p53 gene. Thus, our data suggest that alterations of the p53 gen e at the mutational ''hot spots'' appear to occur infrequently in prim ary human prostate cancer, but may emerge in later stages of tumor pro gression. Furthermore, we confirm that loss of heterozygosity at a loc us telomeric to p53, but not including p53, is associated with metasta tic progression in 1 case.