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前列腺上皮内瘤变和前列腺癌中骨形态发生因子基因剂量异常

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

作者信息

Doak Shareen H, Jenkins Spencer A, Hurle Rhidian A, Varma Murali, Hawizy Azad, Kynaston Howard G, Parry James M

机构信息

School of Medicine, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, Wales, UK.

出版信息

Cancer Genet Cytogenet. 2007 Jul 15;176(2):161-5. doi: 10.1016/j.cancergencyto.2007.03.011.

DOI:10.1016/j.cancergencyto.2007.03.011
PMID:17656261
Abstract

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.

摘要

与良性前列腺组织相比,已有报道称骨形态发生蛋白(BMP)在前列腺癌中存在异常表达。由于基因表达异常通常源于基因拷贝数的改变,我们对早期前列腺癌患者的这种可能性进行了研究。开发了用于BMP、BMP5、BMP7和UC28基因座荧光原位杂交的探针,并将其应用于具有相邻良性上皮、高级别前列腺上皮内瘤变和前列腺癌区域的存档切片。对每个区域的200个细胞核进行了评估。未观察到所检测基因座的缺失,但BMP2、BMP5、BMP7和UC28在58%、50%、50%和67%的肿瘤灶中出现了增益。这些拷贝数异常可能由肿瘤发生早期事件引起,因为它们也存在于10%-30%的高级别前列腺上皮内增生灶中。此外,一个肿瘤显示出UC28基因座的串联扩增。大约一半的前列腺肿瘤显示BMP2、BMP5、BMP7和UC28基因座的拷贝数增加,这可能解释了它们在肿瘤性前列腺组织中的异常基因表达模式。

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