A Methylation-Based Assay for the Detection of Prostate Cancer Cells

前列腺癌是西方世界男性死亡和发病的主要原因。人们对导致前列腺癌发生的早期事件知之甚少，尽管最近的证据表明，被称为甲基化的DNA修饰可能是疾病的早期指标。我们目前的工作表明，在超过90%的前列腺癌中，通过这种DNA修饰，参与细胞解毒的基因(称为GST)被关闭。我们研究了前列腺癌和正常前列腺组织中GST基因的甲基化模式，发现GST基因只在前列腺癌组织中被修饰。这一重要信息使我们能够设计一种测试，通过分析GST修饰来特异性地识别前列腺癌细胞。在这笔赠款中，我们计划进一步优化这项测试，以确保其灵敏度和可靠性。特别是，我们计划将我们基于甲基化的测试与PSA和其他目前用于检测前列腺癌的测试的有效性进行比较。此外，我们计划识别其他基因，这些基因也可能在前列腺癌中通过DNA甲基化而被特异性地关闭。这些数据将允许开发新的标志物和方法来分期前列腺癌和可能的其他癌症的进展。

Prostate Cancer is a major cause of death and morbidity among men in the western world. Little is understood of the early events that lead to the development of prostate cancer though recent evidence suggests that a modification of the DNA called methylation may be an early indictor of disease. Our current work has shown that a gene involved in the detoxification of the cell (called GST) is switched off in over 90% of prostate cancers by this DNA modification. We have studied the methylation pattern of the GST gene in prostate cancer and normal prostate tissue and found that the GST gene is modified exclusively in the cancer tissue . This important information has allowed us to design a test to specifically identify prostate cancer cells by assaying for GST modification . In this grant we plan to further optimise this test to ensure its sensitivity and reliability. In particular we plan to compare the effectiveness of our methylation-based test to the PSA and other tests currently used for the detection of prostate cancer. In addition we plan to identify other genes that also may be switched off specifically in prostate cancer by DNA methylation. This data will allow the development of new markers and approaches to stage the progression of prostate and possibly other cancers.