title: VHL, the story of a tumour suppressor gene.
abstract: Since the Von Hippel-Lindau (VHL) disease tumour suppressor gene VHL was identified in 1993 as the genetic basis for a rare disorder, it has proved to be of wide medical and scientific interest. VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation. Early inactivation of VHL is commonly seen in clear-cell renal cell carcinoma (ccRCC), and insights gained from the functional analysis of pVHL have provided the foundation for the routine treatment of advanced-stage ccRCC with novel targeted therapies. However, recent sequencing studies have identified additional driver genes that are involved in the pathogenesis of ccRCC. As our understanding of the importance of VHL matures, it is timely to review progress from its initial description to current knowledge of VHL biology, as well as future prospects for novel medical treatments for VHL disease and ccRCC.
authors.affiliation: 1] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [3] Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Gossage
authors.affiliation: 1] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.affiliation: 1] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Box 238, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051794:Von Hippel-Lindau Tumor Suppressor Protein