The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy

Measurement of vessel caliber by Magnetic Resonance Imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI coined as Vessel Architectural Imaging (VAI) that exploits an intriguing and overlooked temporal shift in the MR signal forming the basis for vessel caliber estimation and show how this phenomenon can reveal new information on vessel type and function not assessed by any other non-invasive imaging technique. We also show how this biomarker can provide novel biological insights into the treatment of cancer patients. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation levels and reduce vessel calibers in patients with recurrent glioblastomas, and more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies