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DNA Methylation in Urological Cancers

  • Chapter
DNA Methylation and Cancer Therapy

Part of the book series: Medical Intelligence Unit ((MIUN))

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Abstract

Urological cancers are a diverse group with different alterations of DNA methylation. In all urological cancers, DNA hypermethylation of specific genes has been described. In contrast, methylation of repetitive sequences is often diminished, resulting in decreased overall methylation levels (“global hypomethylation”). Altered imprinting is also found. Testicular tumors are derived from more or less immature germ cells whose methylation patterns they often reflect. Subtypes can be distinguished by the extents of global hypomethylation and hypermethylation. Renal cell carcinomas typically display hypermethylation restricted to specific genes important for tumor development and progression. By comparison, methylation patterns are more severely disturbed in prostate and bladder cancers in which hypermethylation of multiple genes coexists with genome-wide hypomethylation. Causes of altered methylation may also differ. Hypermethylation could be incidental in renal cancers, but is more likely caused by primary defects in the methylation machinery in bladder and prostate cancers, which are still undefined. However, potential influences by diet and by chemical carcinogens need to be better understood. DNA hypermethylation acts as an important mechanism in the silencing of tumor suppressor genes. Global hypomethylation often correlates with chromosomal instability. The mechanism underlying this association is not understood. Hypermethylation of multiple genes has been detected in urine, ejaculate, blood and tissue biopsies. DNA methylation assays can improve detection, monitoring, staging and classification of urological cancers and in the near future could be employed to select patient-adapted therapies. In contrast, efficacy, application range and risk of inducing tumor progression of drugs targeting DNA methylation are yet to be determined in urological cancers. The diversity of these cancers require a carefully adapted approach to optimal exploitation of their DNA methylation alterations.

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  1. Department of Urology, Heinrich-Heine-University, Dusseldorf, Germany

    Wolfgang A. Schulz & Hans-Helge Seifert

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Schulz, W.A., Seifert, HH. (2005). DNA Methylation in Urological Cancers. In: DNA Methylation and Cancer Therapy. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27443-X_4

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