ALLELIC LOSSES AT LOCI ON CHROMOSOME-10 ARE ASSOCIATED WITH METASTASIS AND PROGRESSION OF HUMAN PROSTATE-CANCER

DNA samples from tumors and paired normal tissues from 48 patients wit h prostate cancer (stage B, 16 cases; stage C, 14 cases; stage D, 18 c ases) were examined with 26 polymorphic markers spanning chromosome 10 . Allelic losses were observed in 17 of the 46 cases (37%) that were i nformative with at least one of the markers. Detailed deletion mapping identified two distict commonly deleted regions on the long arm of ch romosome 10 (10q22-q24:7cM and 10q25.1:17cM) and one on 10p, suggestin g that at least three tumor suppressor genes associated with prostate cancer are present on this chromosome. We observed loss of heterozygos ity more frequently in tumors from fatal cases (stage D, 8/16, 50%) th an in localized tumors (stage B, 0/16, 0%; P = 0.001 or stage B + C, 5 /30, 17%; P = 0.02 Fisher's exact test). All metastatic tissues showed allelic loss at one or more loci on 10q. In five of the nine patients from whom DNAs were available from both metastatic and primary tumors , the primary cancer foci had no detectable abnormality of chromosome 10, while the metastatic foci showed allelic loss on chromosome 10. Th ese results suggested that inactivation of one or more tumor suppresso r genes on chromosome 10 plays an important role in late stages of pro state cancer. (C) 1996 Wiley-Liss, Inc.