Bone morphogenic factor gene dosage abnormalities in prostatic intraepithelial neoplasia and prostate cancer

Abnormal expression of bone morphogenic proteins (BMP) has been reported in prostate cancer as compared to benign prostatic tissue. Since aberrations in gene expression often result from alterations in gene copy number, we have investigated this possibility in patients with early prostate cancer. Probes for fluorescence in situ hybridization for the BMP, BMP5, BMP7, and UC28 gene loci were developed and applied to archival sections with areas of adjacent benign epithelium, high-grade prostatic intraepithelial neoplasia, and prostate carcinoma. Two hundred nuclei from each region were evaluated. No deletions of the gene loci examined were observed, but gain of BMP2, BMP5, BMP7, and UC28 occurred in 58, 50, 50, and 67% of tumor foci, respectively. These aberrations in copy number may be caused by early events in tumor development because they were also present in 10-30% of high-grade prostatic intraepithelial hyperplasia foci. In addition, one tumor demonstrated a tandem amplification of the UC28 gene locus. Approximately half of the prostate tumors displayed increased copy numbers of the BMP2, BMP5, BMP7, and UC28 gene loci, which may account for their abnormal gene expression patterns in neoplastic prostate tissue.