EXPRESSION OF THE VONHIPPEL-LINDAU TUMOR-SUPPRESSOR GENE, VHL, IN HUMAN FETAL KIDNEY AND DURING MOUSE EMBRYOGENESIS

Background: Von Hippel-Lindau (VHL) disease is a familial cancer syndr ome that has a dominant inherited pattern which predisposes affected i ndividuals to a variety of tumors. The most frequent tumors are hemang ioblastomas of the central nervous system and retina, renal cell carci noma (RCC), and pheochromocytoma. The recent identification and charac terization of the VHL gene on human chromosome 3p and mutational analy ses confirms the VHL gene functions as a classical tumor suppressor. N ot only are mutations in this gene responsible for the VHL syndrome, b ut mutations are also very frequent in sporadic RCC. Materials and Met hods: VHL expression in human kidney and during embryogenesis, was ana lyzed by in situ mRNA hybridization with S-35-labeled antisense VHL pr obes, derived from human and mouse cDNAs, on cryosections of human fet al kidney and paraffin sections of murine embryos. Results: Ln human f etal kidney, there was enhanced expression of VHL within the epithelia l lining of the proximal tubules. During embryogenesis, VHL expression was ubiquitous in all three germ cell layers and their derivatives. E xpression occurred in the cerebral cortex, midbrain, cerebellum, retin a, spinal cord, and postganglionic cell bodies. All organs of the thor acic and abdominal cavities expressed VHL, but enhanced expression was most apparent in the epithelial components of the lung, kidney, and e ye. Conclusions: In human fetal kidney, the enhanced epithelial expres sion of the VHL gene is consistent with the role of this gene in RCC. There is widespread expression of the VHL gene during embryogenesis, b ut this is pronounced in areas associated with VHL phenotypes. These f indings provide a histological framework for investigating the physiol ogical role of the VHL gene and as basis for further mutational analys is.