Von Hippel-Lindau genetics

Genetic linkage studies in families with the von Hippel-Lindau syndrome indicate that the gene involved in the von Hippel-Lindau suppressor protein (pVHL) is on chromosome 3p25:

• pVHL - this has been shown to bind directly to the alpha subunits of the heterodimeric transcription factor HIF (hypoxia inducible factor)
• pVHL directs the polyubiquitination and, hence, destruction of HIF in the presence of oxygen
• loss of pVHL function leads to deregulation of HIF target genes (these play critical roles in angiogenesis)

Note that:

• 85% of all tumours of the renal parenchyma have mutations of the VHL gene
• 67% of all renal adenocarinomas have mutations of the VHL gene

Reference:

1. Ivan M, Kaelin WG (2001). The von Hippel-Lindau tumor suppressor protein. Curr Opin Genet Dev.11(1):27-34.
2. Karp, J.E. & Broder, S. (1995). Molecular foundations of cancer: new targets for intervention. Nature Med. 1(4), 309-320
3. Iliopoulos, O. et al. (1995). Tumour suppression by the human von Hippel-Lindau gene product. Nature Med. 1(8), 822-826