GENETIC CHANGES IN PRIMARY AND RECURRENT PROSTATE-CANCER BY COMPARATIVE GENOMIC HYBRIDIZATION

Genetic changes leading to the development of prostate cancer and fact ors that underlie the clinical progression of the disease are poorly c haracterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genet ic markers of tumor progression. CGH analysis indicated that 74% of pr imary prostate carcinomas showed DNA sequence copy number changes. Los ses were 5 times more common than gains and most often involved 8p (32 %), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic l oss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance wit h CGH results. In local recurrences that developed during endocrine th erapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (foun d in 89% of recurrences versus 6% of primary tumors), X (56% versus 0% ), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), bei ng particularly often involved. In conclusion, our CGH results indicat e that losses of several chromosomal regions are common genetic change s in primary tumors, suggesting that deletional inactivation of putati ve tumor suppressor genes in these chromosomal sites is likely to unde rlie development of prostate cancer. Furthermore, the pattern of genet ic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. Thes e chromosome aberrations may have diagnostic utility as markers of pro state cancer progression.