Goessl C, Krause H, Müller M, Heicappell R, Schrader M, Sachsinger J, Miller K
Department of Urology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Cancer Res. 2000 Nov 1;60(21):5941-5.
Promoter hypermethylation of the glutathione S-transferase P1 gene (GSTP1) is the most frequent DNA alteration in prostatic carcinoma. Because this epigenetic DNA alteration can be reliably detected by methylation-specific PCR (MSP), we applied this new technique for molecular detection of prostate cancer in various human bodily fluids. We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, ejaculate, and urine after prostate massage and from prostate carcinoma tissues from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Fluorescently labeled MSP products were analyzed on an automated gene sequencer. Whereas GSTP1 promoter hypermethylation was not detectable by MSP in prostate tissue and bodily fluids from patients with BPH, we found it in 94% of tumors (16 of 17), 72% of plasma or serum samples (23 of 32), 50% of ejaculate (4 of 8) and 36% of urine (4 of 11) from patients with prostate cancer. Additionally, MSP identified circulating tumor cells in 30% (10 of 33) of prostate cancer patients. Analysis of GSTP1 promoter hypermethylation by MSP thus provides a specific tool for molecular diagnosis of prostate cancer in bodily fluids.
谷胱甘肽S-转移酶P1基因（GSTP1）启动子高甲基化是前列腺癌中最常见的DNA改变。由于这种表观遗传的DNA改变可通过甲基化特异性PCR（MSP）可靠地检测到，我们将这项新技术应用于在各种人体体液中对前列腺癌进行分子检测。我们研究了从血浆、血清、射精液、前列腺按摩后的尿液以及33例前列腺癌患者和26例良性前列腺增生（BPH）对照患者的前列腺癌组织中分离出的DNA中的GSTP1启动子高甲基化情况。对荧光标记的MSP产物在自动基因测序仪上进行分析。在BPH患者的前列腺组织和体液中，MSP检测不到GSTP1启动子高甲基化，但在前列腺癌患者的94%的肿瘤（17例中的16例）、72%的血浆或血清样本（32例中的23例）、50%的射精液（8例中的4例）和36%的尿液（11例中的4例）中发现了这种情况。此外，MSP在30%（33例中的10例）的前列腺癌患者中鉴定出循环肿瘤细胞。因此，通过MSP分析GSTP1启动子高甲基化可为在体液中对前列腺癌进行分子诊断提供一种特异性工具。
