Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.

Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. 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 genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses 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 loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found 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%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic 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. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.

Genetic alterations in prostate cancer cell lines detected by comparative genomic hybridization.

Recent studies have identified several chromosomal regions that are altered in prostate cancer. However, the specific genes affected are, in most of the cases, not known. Cancer cell lines could provide a valuable resource for cloning of genes that are commonly affected in cancer. The first step in the identification of such genes is the detection of chromosomal aberrations. Here, we have used comparative genomic hybridization (CGH) to screen for genetic alterations in four prostate cancer cell lines, LNCaP, DU145, PC-3, and TSU-Pr1. The analysis showed that, except for the LNCaP, these cell lines contained many genetic changes (> or = 10 per cell line), suggesting that they resemble genetically more closely hormone-refractory or metastatic than primary prostate carcinomas. All the chromosomal regions that have been implicated in prostate cancer were altered in at least one of the cell lines. The most common genetic changes were gain at 11q and losses at 6q, 9p, and 13q, each present in at least three cell lines. Identification of genetic aberrations by CGH in these cell lines should facilitate the choice of individual cell lines for cloning of genes that are involved in the development and progression of prostate cancer.