ALLELIC LOSSES ON 18Q21 ARE ASSOCIATED WITH PROGRESSION AND METASTASIS IN HUMAN PROSTATE-CANCER

We analyzed normal/tumor DNA pairs obtained from 46 patients with pros tate cancers (stage B, 16 cases; C, 10 cases; D1, 4 cases; and endocri ne therapy-resistant cancer-death, 16 cases) for loss of heterozygosit y using 32 microsatellite markers on chromosome 18. Seventeen of the 4 6 cases (37%) showed loss of heterozygosity (LOH) for at least one loc us on the long arm. Detailed deletion mapping in these rumors identifi ed a distinct commonly deleted region within a 5-cM interval on l8q21. 1. There was a statistical correlation between the frequency of LOH on 18q and clinical stage (X-2 = 12.3; P = 0.0064). LOH on 18q was obser ved more frequently in Stage D1 cases (4/4; 100%) than in Stage B + C cases (5/26; 19%; P = 0.0046, Fisher's exact test). In 8 of 9 (89%) ca ncer-death patients from whom DNAs were available from both primary an d metastatic tumors, the primary tumors had either no detectable abnor mality of chromosome 18 or the region involving loss of heterozygosity was limited while the metastatic foci showed more frequent and extend ed allelic losses on this chromosome. No abnormalities were detected i n the DCC and DPC4 genes when their exons were analyzed separately by single strand conformation polymorphism assay. These results suggest t hat inactivation of one or more putative tumor suppressor genes on 18q 21 other than DCC and DPC4 plays an important role in the progression of human prostate canter. (C) 1997 Wiley-Liss, Inc.