title: Von Hippel-Lindau disease.
abstract: Von Hippel-Lindau (VHL) disease is an uncommon, autosomal dominant hereditary multitumor syndrome caused by germline alterations of the VHL gene, which has been cloned recently and identified as a tumor suppressor gene. The major lesions in VHL disease include hemangioblastomas in the central nervous system and retina, clear cell renal cell carcinomas, pheochromocytomas, pancreatic tumors, epididymal cystadenomas, endolymphatic sac tumors, carcinoid tumors, and multiple cysts of the kidney, pancreas, and epididymis. Compared with sporadic ones, the tumors in VHL disease develop at an earlier age and often multifocally. Histologic features of VHL tumors are characterized by their high degree of vascularization and the presence of a clear cell component. Hypervascularization is induced by overexpression of vascular endothelial growth factor (VEGF), and because the principal function of VHL protein is the negative regulation of hypoxia-inducible mRNAs including VEGF mRNA, inactivation of VHL gene plays critical roles in angiogenesis of the VHL tumors. In addition, since VHL protein is also required for the down-regulation of transcription activity of certain genes for the cell growth and cell cycle, inactivation of VHL gene may contribute to tumorigenesis of the VHL tumors. A significant difference in the frequency of types of VHL gene mutation has been noted among the affected families, known as the genotype-phenotype correlations.
authors.affiliation: Department of Pathology, University of Tokushima School of Medicine, Tokushima 770-8503, Japan. sano@basic.med.tokushima-u.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Horiguchi
mesh_terms: D016543:Central Nervous System Neoplasms / Q000098:blood supply / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D018325:Hemangioblastoma / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008025:Ligases / Q000235:genetics*; D008222:Lymphokines / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human