Antony P, Rose M, Gaisa N T, Alkaya S, Heidenreich A, Knüchel R, Dahl E
Institut für Pathologie, Arbeitsgruppe Molekulare Onkologie, Universitätsklinikum der RWTH Aachen, Aachen.
Pathologe. 2010 Oct;31 Suppl 2:244-50. doi: 10.1007/s00292-010-1367-1.
Despite considerable advances in recent years in our understanding of the genetic changes occurring in urinary bladder cancer, similar progress in the field of epigenetics has hitherto been lacking. Increasingly, however, focus has shifted in the direction of aberrant DNA methylation as a result of recent studies showing the direct impact of such promoter hypermethylation on the loss of tumor suppressor gene expression and function, therefore potentially affecting tumor genesis and progression. The purpose of this study is the identification and characterization of new DNA methylation markers in urinary bladder cancer, with the expectation that these markers could then be incorporated in a multi-gene panel for clinical use in early cancer detection. In addition, better understanding of the signalling pathways involved will undoubtedly impact the development of new treatment strategies. Potential candidate genes, including the Wnt antagonist SFRP5 among others, will be validated by different epigenetic techniques using invasive and superficial urothelial cell lines as well as tumor and urine samples from bladder cancer patients.
尽管近年来我们对膀胱癌发生的基因变化的理解有了相当大的进展,但表观遗传学领域迄今仍缺乏类似的进展。然而,由于最近的研究表明这种启动子高甲基化对肿瘤抑制基因表达和功能丧失有直接影响,因此越来越多的研究重点转向了异常DNA甲基化,这可能会影响肿瘤的发生和进展。本研究的目的是鉴定和表征膀胱癌中的新DNA甲基化标志物,期望这些标志物随后可纳入多基因检测板,用于早期癌症检测的临床应用。此外,更好地理解所涉及的信号通路无疑将影响新治疗策略的开发。潜在的候选基因,包括Wnt拮抗剂SFRP5等,将通过不同的表观遗传技术,使用侵袭性和浅表性尿路上皮细胞系以及膀胱癌患者的肿瘤和尿液样本进行验证。