Histone

Gene

microRNA

Epigenetic therapy

Biology

Epigenetics

Somatic cell

Cancer research

DNA methylation

Renal cell carcinoma

Genetics

Bioinformatics

Internal medicine

Oncology

Medicine

Cell

Carcinogenesis

Disease

Cancer

Gene expression

Reprogramming

Pathology

Nature Reviews Urology

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–β-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. Joosten et al. review the main epigenetic alterations involved in renal carcinogenesis and their effects on key signalling pathways. The authors also discuss the utility of epigenetic aberrations as renal cancer biomarkers and their potential as treatment targets.

Epigenetics in renal cell cancer: mechanisms and clinical applications