LOCALIZATION OF A TUMOR-SUPPRESSOR GENE ASSOCIATED WITH PROGRESSION OF HUMAN PROSTATE-CANCER WITHIN A 1.2 MB REGION OF 8P22-P21.3

Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8, In order to take a step toward isola tion of the putative tumor suppressor gene(s) on 8p via positional clo ning, we performed high-resolution deletion mapping in 46 prostate can cers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length poly morphism markers for this chromosomal region. Allelic losses were obse rved in 25 of the 44 cases (57%) that were informative with at least o ne locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Alle lic losses on 8p were observed more frequently in the cancer death cas es (14/17, 82%) than in early-stage tumors (11/27, 40%; 8 < 0.01, Fish er's exact test). In two our of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tum ors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results sug gest that inactivation of tumor suppressor genes on 8p plays an import ant role in the progression of prostate cancer. (C) 1995 Wiley-Liss, I nc.