MOLECULAR ANALYSIS OF THE INK4 FAMILY OF GENES IN PROSTATE CARCINOMAS

Purpose: A newly recognized class of INK4 family of cyclin-dependent k inase inhibitors CDKIs) include its prototype, p16 (INK4A/MTS1/CDKN2), and three others, p15 (INK4B/MTS2), p18 (INK4C), and p19 (INK4D). The putative tumor suppressor gene, p16 is frequently altered in certain neoplasms and many cell lines. The potential role of INK4 CDKIs in pat hogenesis of prostate carcinoma was studied. Materials and Methods: Th irty-two primary prostate cancer samples and two prostate cancer cell lines were examined for alterations of the p16, p15, p18, and p19 gene s by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and Southern blot analysis. Results: Alteration of the p16 gene was found in one of 32 primary prostate cancer samples by PCR-SS CP. DNA sequencing of the sample showed a 24-basepair insertion in exo n 1 of the p16 gene at codon 11. No other mutations were found in p15, p18, or p19 genes by PCR-SSCP. Furthermore, none of the p16, p15, p18 , or p19 genes had alterations by Southern blot analysis. Conclusions: These results indicate that structural abnormalities of the INK4 CDKI s is a rare event in prostate carcinoma, and the loss of function of I NK4 CDKIs by other mechanisms, such as methylation should be further e xplored.