A clearer view of the molecular complexity of clear cell renal cell carcinoma.
The von Hippel-Lindau (VHL) tumor suppressor gene is mutated as an early event in almost all cases of clear cell renal cell carcinoma (ccRCC), the most frequent form of kidney cancer. In this review we discuss recent advances in understanding how dysregulation of the many hypoxia-inducible factor α-dependent and -independent functions of the VHL tumor suppressor protein (pVHL) can contribute to tumor initiation and progression. Recent evidence showing extensive inter- and intratumoral genetic diversity has given rise to the idea that ccRCC should actually be considered as a series of molecularly related, yet distinct, diseases defined by the pattern of combinatorial genetic alterations present within the cells of the tumor. We highlight the range of genetic and epigenetic alterations that recur in ccRCC and discuss the mechanisms through which these events appear to function cooperatively with a loss of pVHL function in tumorigenesis.
Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich CH-8057, Switzerland; email: ian.frew@access.uzh.ch.
Ian J
IJ
Frew
Holger
H
Moch
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
D051794:Von Hippel-Lindau Tumor Suppressor Protein
HIFα; VHL; genomics; kidney cancer; pathology