p53 mutations in prostate cancer bone metastases suggest that selected p53mutants in the primary site define foci with metastatic potential

Purpose: This study was undertaken to establish the pattern of specific p53 gene mutations in prostate cancer within primary tumors and distant metast ases. Materials and Methods: We performed polymerase chain reaction-single-strand conformation polymorphism and sequencing analyses of p53 exons 5-8 in DNA extracted from 22 formalin-fixed, paraffin-embedded tissues from 17 patient s. Samples fi om three patients included specimens from primary and metasta tic sites (paired specimens). Results: G:C-to-A:T transitions were the most common point mutations (64%). Six (55%) of 11 G:C-to-A:T transitions occurred at CPG dinucleotides in fi ve hot-spot codons (175, 245, 248, 273, and 282). Sequencing analysis of th e paired samples revealed that two of the three pairs had the same mutation in both. Sequencing analysis of DNA from a different area of one of the pr imary tumors revealed a different mutation in the p53 gene. Conclusions: Our results suggest that specific p53 mutations participate in the progression of human prostate cancer. These findings support those of others that indicate that the primary cancer is heterogeneous and clonal ex pansion occurs during the progression of clinically detectable prostate can cer. Our data also imply that p53 mutations at the primary site may be pred ictive of metastases.