Molecular detection of prostate cancer in urine by GSTP1 hypermethylation.
Molecular detection of prostate cancer in urine by GSTP1 hypermethylation.
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发表时间：
2001-09
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通讯作者：
P. Cairns;M. Esteller;J. Herman;M. Schoenberg;C. Jerónimo;M. Sanchez-Cespedes;N. Chow;Marc E. Grasso-Marc
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作者：
P. Cairns;M. Esteller;J. Herman;M. Schoenberg;C. Jerónimo;M. Sanchez-Cespedes;N. Chow;Marc E. Grasso-Marc
前列腺癌的早期发现和治疗迫切需要新的方法。克隆性遗传改变已被用作检测多种癌症类型体液中肿瘤细胞的靶点。类似的前列腺癌分子诊断策略需要常见的和/或早期的基因改变作为肿瘤前列腺癌细胞的特异性靶点。在大多数(90%)原发性前列腺癌中发现了谷胱甘肽S转移酶p1基因调控序列的高甲基化，而在正常前列腺组织或其他正常组织中未发现。我们推测前列腺癌患者的尿液中可能含有脱落的肿瘤细胞或DNA分析碎片。采集28例临床分期可治愈的前列腺癌患者的原发肿瘤标本、外周血淋巴细胞(正常对照)和单纯性排尿标本。提取基因组DNA，用甲基化特异性聚合酶链式反应盲法检测GSTP1的甲基化状态。结果显示，28例前列腺癌中有22例(79%)GSTP1甲基化阳性。在22例患者中，6例(27%)尿沉渣DNA GSTP1甲基化阳性，提示尿液中存在肿瘤DNA。此外，当相应的肿瘤为阴性时，没有尿沉渣DNA含有甲基化的情况。虽然我们只在不到三分之一的尿液样本中检测到GSTP1甲基化，但我们已经证明了尿液中前列腺癌的分子诊断是可行的。更大规模的研究集中在肿瘤大小、前列腺癌的位置、尿液采集技术以及更敏感的技术上，可能会导致GSTP1超甲基化在前列腺癌诊断和治疗中的有用应用。
Novel approaches for the early detection and management of prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many cancer types. A similar strategy for molecular diagnosis of prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from prostate cancer patients might contain shed neoplastic cells or debris amenable to DNA analysis. Matched specimens of primary tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with prostate cancer of a clinical stage amenable to cure. Genomic DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment DNA was positive for GSTP1 methylation, indicating the presence of neoplastic DNA in the urine. Furthermore, there was no case where urine-sediment DNA harbored methylation when the corresponding tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate neoplasia in urine is feasible. Larger studies focusing on carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in prostate cancer diagnosis and management.