High frequency of deletion on chromosome 9p21 may harbor several tumor-suppressor genes in human prostate cancer

Chromosome 9p has been reported to be a critical region of loss in various cancers. Our present study was designed to determine the frequency of delet ions at: different loci of chromosome 9p in microdissected samples of norma l prostatic epithelium and carcinoma from the same patients. For this purpo se, DNA was extracted from the microdissected sections of normal and tumor cells of 40 prostate specimens, amplified by PGR and analyzed for loss of h eterozygosity (LOH) on chromosome 9p using 15 microsatellite markers. Only 6 of 15 microsatellite markers exhibited LOH in prostate cancer specimens ( D9S162, D9S1748, D9S171, D9S270, D9S273 and D9S 153). LOH on chromosome 9p was identified in 29 of 40 cases (72.5%) with at least 1marker. The main de letion was found on 9p21, at loci D9S1748 (50%), D9S171 (51.4%) and D9S270 (21.8%). There was also a deletion on 9p22 at locus D9S 162(8.3%), on 9p13 at locus D9S273 (13.8%) and on 9p11 at: locus D9S153 (7.7%). LOH data were correlated with stage of prostate cancer and revealed a high frequency of L OH at 3 or more loci in samples with stage T3N0M0 (46%) compared with stage T2N0M0 (15%), which suggests a higher incidence of LOH in the advanced sta ge of prostate cancer. One of the candidate target tumor-suppressor genes, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in tu mor cell lines, Expression of P16 protein was either absent or very low in prostate cancer samples, suggesting that loss of the P16 gene may be involv ed in prostatic carcinogenesis. (C) 1999 Wiley-Liss.