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Review

Nature Reviews Cancer 2, 673–682 (1 September 2002) | doi:10.1038/nrc885

Molecular basis of the VHL hereditary cancer syndrome

William G. Kaelin

The von Hippel–Lindau hereditary cancer syndrome was first described about 100 years ago. The unusual clinical features of this disorder predicted a role for the von Hippel–Lindau gene (VHL) in the oxygen-sensing pathway. Indeed, recent studies of this gene have helped to decipher how cells sense changes in oxygen availability, and have revealed a previously unappreciated role of prolyl hydroxylation in intracellular signalling. These studies, in turn, are laying the foundation for the treatment of a diverse set of disorders, including cancer, myocardial infarction and stroke.