Analysis of DNA methylation in cancer : location revisited

Changes in DNA methylation in cancer have been heralded as promising targets for the development of powerful diagnostic, prognostic, and predictive biomarkers. Despite the existence of more than 14,000 scientific publications describing DNA methylation-based biomarkers and their clinical associations in cancer, only 14 of these biomarkers have been translated into a commercially available clinical test. Methodological and experimental obstacles are both major causes of this disparity, but the genomic location of a DNA methylation-based biomarker is an intrinsic and essential property that also has an important and often overlooked role. Here, we examine the importance of the location of DNA methylation for the development of cancer biomarkers, and take a detailed look at the genomic location and other relevant characteristics of the various biomarkers with commercially available tests. We also emphasize the value of publicly available databases for the development of DNA methylation-based biomarkers and the importance of accurate reporting of the full methodological details of research findings

Epigenetics in renal cell cancer: mechanisms and clinical applications

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