Role of VHL tumor suppressor gene in central nervous system

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Von Hippel-Lindau disease (VHL) is an autosomal dominant hereditary disease which develops hamangioblastomas in the central nervous system and retina, renal cell carcinoma, and pheochromocytoma. The causative gene has been isolated from chromosome 3p in 1993. We have found somatic VHL gene mutations in not only sporadic hemangioblastomas and renal cell but also gliomas. In addition, we have performed molecular genetic diagnosis of 80 Japanese VHL families by the DNA analyses. The expressions of VHL gene and product were identified at neuron in the central nervous system and proximal renal tubule as well as cytoplasm of hemangiobalstoma and glioma. However, pathologically more malignant gliomas showed less expression of VHL gene produst. In process of neuronal development, VHL gene expressions were correlated with neuronal differentiation in neural stem cells. In addtion, it was suggested that cell cycle of neural stem cells were down-regulated by VHL gene.