Epigenetics of urothelial carcinoma

Methods Mol Biol. 2015;1238:183-215. doi: 10.1007/978-1-4939-1804-1_10.

Abstract

Urothelial carcinoma is the most frequent type of bladder cancer. Improvements in diagnostics and therapy of this common tumor are urgently required and need to be based on a better understanding of its biology. Epigenetic aberrations are crucial to urothelial carcinoma development and progression. They affect DNA methylation, histone modifications, chromatin remodeling, long noncoding RNAs, and microRNAs. Compared to other cancers, DNA hypomethylation, especially at LINE-1 retrotransposons, and mutations in enzymes establishing or removing histone acetylation or methylation are particularly prominent. Accumulating evidence suggests that disturbances in DNA methylation, histone modifications and noncoding RNAs may contribute especially to altered differentiation and metastatic potential. With proper selection, histone-modifying enzymes may constitute good targets for therapy. For diagnostics, DNA methylation and miRNA biomarkers are well suited because of their relatively high stability. There are indeed excellent biomarker candidates for DNA-methylation-based diagnostics of urothelial carcinoma, whereas miRNAs are well investigated, but there are still many discrepancies between studies published to date.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Methylation
  • Epigenomics / methods*
  • Histones / genetics
  • Humans
  • RNA, Untranslated / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urothelium*

Substances

  • Histones
  • RNA, Untranslated