High-resolution array comparative genomic hybridization of chromosome arm 8q: evaluation of genetic progression...

Copy number increase of 8q has previously been shown to be associated with a poor clinical outcome and tumor recurrence in patients with prostate cancer. In this study, a detailed genomic analysis of 8q was performed of archival primary and metastatic prostatic adenocarcinomas (n = 22), and prostate cancer xenografts (n = 9), and cell lines (n = 3). We performed array comparative genomic hybridization (aCGH) using a whole chromosome arm contig array consisting of 702 8q-specific BAC clones. Five regions of frequent copy number increase were identified, i.e. at chromosome bands 8q21.13 (81-82 Mb), 8q22.1 (94-96 Mb), 8q22.2-3 (101-103 Mb), 8q24.13 (124-126 Mb), and 8q24.21 (127-129 Mb), the most distal region containing the MYC oncogene. MYC and 13 genes of the other four regions with putative relevance to cancer were selected. Two additional genes were derived from high-level amplifications detected by 8q aCGH analysis of prostate cancer xenograft PC339. Quantitative RT-PCR of these 16 genes was performed in a series of 26 prostate specimens, including normal tissue (n = 5), fresh-frozen adenocarcinoma (n = 7), cancer xenograft (n = 9), and cancer cell line material (n = 2). Three of the 16 genes were significantly overexpressed in cancer compared with that in normal prostate tissue, i.e. PDP, located at 8q22.1 (95 Mb), PABPC1 located at 8q22.3 (102 Mb), and KIAA0196 located at 8q24.13 (126 Mb). These genes can be considered putative progression markers for prostate cancer.