FOCAL DISTRIBUTION OF P16 CDKN2 GENE-MUTATIONS WITHIN INDIVIDUAL PROSTATE CARCINOMAS/

To examine the potential role of pl6/CDKN2 gene mutations in prostate tumorigenesis, focal areas within individual tumors were investigated. Eleven cases of histologically heterogeneous prostate carcinomas obta ined by radical prostatectomy were subjected to analysis of p16/CDKN2 gene mutations. DNA was extracted from 5 to 10 separate areas of each tumor with different growth or histological patterns. Exons 1 through 3 of the p16/CDKN2 gene were amplified using the polymerase chain reac tion (PCR) and screened for homozygous deletions and mutations of this gene by single-strand conformation polymorphism (SSCP) analysis. No h omozygous deletions were observed in any of the prostate carcinomas, b ut two of the eleven tumors demonstrated mutations in exon 2 of p16/CD KN2 gene. Missense mutations were detected in only one and two foci, r espectively, out of six ana ten selected tumor areas. The present resu lts suggest that p16/CDKN2 gene mutations, although they occur at a lo w incidence, are involved in prostate tumorigenesis, indicating a muta tional heterogeneity in addition to morphological heterogeneity.