Andrés G, Ashour N, Sánchez-Chapado M, Ropero S, Angulo J C
Servicio de Urología, Hospital Universitario de Getafe, Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Universidad Europea de Madrid, Getafe, Madrid, España.
Actas Urol Esp. 2013 Jun;37(6):368-75. doi: 10.1016/j.acuro.2013.03.001. Epub 2013 May 1.
We have synthesized the principal advances in the field of the study of epigenetics and specifically DNA methylation regarding the diagnosis of urological neoplasms.
Review of the literature (PubMed, MEDLINE and Cochrane) on the study of DNA methylation in urological neoplasms (prostate cancer, bladder cancer, renal cancer and testicular cancer), considering all the studies published up to January 2013.
It was possible to determine the state of methylation of many genes in our tumor samples. When these were compared with healthy tissue samples, it was possible to define the specific aberrant methylation patterns for each type of tumor. The study and definition of specific abnormal methylation patterns of each type of tumor is a tool having potential utility for diagnosis, evaluation, prediction of prognosis and treatment of the different forms of genitourinary cancer. The analysis of gene methylation in urine after micturition or post-prostatic massage urine, semen, in the wash plasma or fluid from prostatic biopsies may allow early detection of bladder, prostate, renal and testicular cancer. In each one of the neoplasms, an epigenetic signature that may be detected in the DNA has been identified, obtained from very scarce or not at all invasive specimens, with potential in the diagnosis and evaluation of prognosis. Validation of these studies will confirm the accuracy, effectiveness and reproducibility of the results available up to now. Criteria have still not been developed that determine if a gene panel provides sufficient information in the health care practice to guide an unequivocal diagnosis or therapeutic conduct. More studies are needed to compare sensitivity, specificity, positive and negative predictive value of the test in each case. Multicenter studies analyzing the real reproducibility of these results in a clinical setting also do not exist.
The study of aberrant DNA methylation in biological specimens of patients has an enormous potential for the early diagnosis and screening of genitourinary neoplasms. A larger number of studies is needed to be able to define the series of genes that would mean unequivocal signatures of malignancy. This methodology also has potential when defining prognostic groups and potential of response to different therapies.
我们总结了表观遗传学领域，特别是DNA甲基化在泌尿系统肿瘤诊断方面的主要进展。
检索了关于泌尿系统肿瘤（前列腺癌、膀胱癌、肾癌和睾丸癌）DNA甲基化研究的文献（PubMed、MEDLINE和Cochrane），纳入截至2013年1月发表的所有研究。
我们能够确定肿瘤样本中许多基因的甲基化状态。将这些样本与健康组织样本进行比较时，可以确定每种肿瘤类型的特定异常甲基化模式。研究和定义每种肿瘤类型的特定异常甲基化模式是一种对不同形式的泌尿生殖系统癌症的诊断、评估、预后预测和治疗具有潜在实用价值的工具。对排尿后尿液、前列腺按摩后尿液、精液、冲洗血浆或前列腺活检液中的基因甲基化进行分析，可能有助于早期发现膀胱癌、前列腺癌、肾癌和睾丸癌。在每种肿瘤中，均已鉴定出一种可在DNA中检测到的表观遗传特征，该特征可从非常稀少或完全无创的样本中获得，具有诊断和预后评估潜力。这些研究的验证将证实目前所得结果的准确性、有效性和可重复性。目前仍未制定出确定基因检测组合在医疗实践中是否能提供足够信息以指导明确诊断或治疗行为的标准。需要更多研究来比较每种情况下检测的敏感性、特异性、阳性和阴性预测值。也不存在分析这些结果在临床环境中真实可重复性的多中心研究。
对患者生物样本中异常DNA甲基化的研究在泌尿生殖系统肿瘤的早期诊断和筛查方面具有巨大潜力。需要进行更多研究，以便能够确定一系列意味着明确恶性特征的基因。这种方法在定义预后组以及对不同治疗的反应潜力方面也具有潜力。
