Epigenetics in renal cell cancer: mechanisms and clinical applications

Sophie C. Joosten, Kim M. Smits, Maureen J. Aarts, Veerle Melotte, Alexander Koch, Vivianne C. Tjan-Heijnen, Manon van Engeland*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

69 Citations (Web of Science)

Abstract

Renal cell carcinoma (RCC) is characterized by an infrequent number of somatic mutations. By contrast, epigenetic aberrations are commonly found in RCC, indicating that epigenetic reprogramming is an important event in RCC development. Epigenetic alterations comprise several different aberrations, such as changes in histone modifications, DNA methylation, and microRNA levels, and occur in the most important signalling pathways in RCC, such as the von Hippel-Lindau disease tumour suppressor (VHL)-hypoxia-inducible factor (HIF) pathway, the WNT-beta-catenin pathway, and pathways involved in epithelial-mesenchymal transition. Owing to their involvement in these pathways and frequent occurrence in RCC, epigenetic alterations are regarded as potential biomarkers for the early detection of disease and for prediction of prognosis and treatment response. In addition, most of these alterations are potentially reversible, so they also provide new targets for therapy. At the moment, epigenetic biomarkers for RCC are not being used in clinical practice, but targeted epigenetic therapies are under investigation. Understanding the extent of epigenetic changes occurring in RCC and the mechanisms by which they influence disease progression and treatment response, as well as knowledge of current research on biomarkers and treatments, is crucial to successful clinical translation of epigenetics in RCC.
Original languageEnglish
Pages (from-to)430-451
Number of pages22
JournalNature Reviews Urology
Volume15
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • TUMOR-SUPPRESSOR GENE
  • LONG NONCODING RNA
  • CPG ISLAND METHYLATION
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • HISTONE DEACETYLASE INHIBITOR
  • ENDOTHELIAL GROWTH-FACTOR
  • PROMOTER HYPERMETHYLATION PROFILE
  • POTENTIAL THERAPEUTIC TARGET
  • INTEGRATED STAGING SYSTEM
  • COMPETING ENDOGENOUS RNA

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