Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors

摘要

Author summary Cancer is generally caused by a series of mutations accumulating over time in a healthy tissue, which becomes re-programmed to proliferate at the expense of the hosting organism. This process is difficult to follow and understand as events in a multitude of different genes can lead to similar outcomes without apparent cause. The von Hippel-Lindau (VHL) tumor suppressor is one of the few genes harboring a familiar cancer syndrome, i.e. VHL mutations are known to cause a predictable series of events leading cancer in the kidneys and a few selected other tissues. This article describes a large-scale analysis to relate known VHL mutations to specific cancer pathways by looking at the molecular interactions. Different cancer types appear to be caused by mutations changing the surface of specific parts of the VHL protein. By looking at the VHL interactors involved, it is therefore possible to identify other candidate genes for mutations leading to very similar cancer types.