LOSS OF HETEROZYGOSITY OF CHROMOSOME-8 MICROSATELLITE LOCI IMPLICATESA CANDIDATE TUMOR-SUPPRESSOR GENE BETWEEN THE LOCI D8S87 AND D8S133 IN HUMAN PROSTATE-CANCER

To search for specific chromosome 8 aberrations in human prostate canc er, DNA was isolated from 44 human prostate tumor samples. Twenty six tumor samples were obtained from locally progressive tumors by transur ethral resection, 12 were from radical prostatectomy specimens, and 6 were from lymph node metastases. Tumor DNAs were screened for allelic losses using 16 highly polymorphic microsatellite loci (14 covering th e p arm, 2 on the q arm). In general, the detected deletions were larg e. In 59% of the tumor DNAs, allelic loss of 3 or more 8p loci was obs erved. Loss of 8p loci occurred in between 36 and 69% of the informati ve cases; for the two 8q markers, the percentages of loss were 11 and 25%, respectively, indicating preferential loss of (part of) gp. In on e tumor, two separate 8p deletions were found. The percentage of loss of heterozygosity was considerably higher in transurethral resection ( 65%) and lymph node metastases (83%) than in radical prostatectomy spe cimens (33%), suggesting that 8p deletion is a relatively late step in tumor progression. The maximal overlapping deleted region in all tumo r DNAs is between the distal locus D8S133 and the proximal locus D8S87 , indicating the localization of a candidate tumor suppressor gene wit hin this region.