BACKGROUND/AIMS Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. METHODS The potential relevant papers were searched via P...

Von Hippel-Lindau (VHL) disease is an autosomal dominant disease that produces a variety of tumors and cysts in the central nervous system and visceral organs, including renal cell carcinoma (RCC). RCC in patients with VHL disease does not frequently metastasize, therefore, the response to treatment and prognosis of metastatic RCC developed in patients with VHL disease has not been reported. Su...

PURPOSE Tumor hypoxia is a major limiting factor for radiation therapy. Hypoxia-inducible factors (HIFs) are overexpressed in several human cancers and are considered prognostic markers and potential targets for cancer therapy. The purpose of the present study was to investigate the impact of HIFs on radiosensitivity. EXPERIMENTAL DESIGN Renal clear cell carcinoma (RCC) cell lines overexpress...

OBJECTIVES To characterize the germline mutations found in a large population of persons having von Hippel-Lindau (VHL) disease mutations with the clinical characteristics of associated retinal capillary hemangioblastomas (RCHs), to measure the prevalence of RCHs among patients with VHL disease generally and specifically for each genotype category, to establish genotype-phenotype correlations b...

Mutations in the von Hippel-Lindau (VHL) gene are pathogenic in VHL disease, congenital polycythaemia and clear cell renal carcinoma (ccRCC). pVHL forms a ternary complex with elongin C and elongin B, critical for pVHL stability and function, which interacts with Cullin-2 and RING-box protein 1 to target hypoxia-inducible factor for polyubiquitination and proteasomal degradation. We describe a ...

The germ-line loss-of-function VHL(R200W) mutation is common in Chuvashia, Russia and occurs in other parts of the world. VHL(R200W) homozygotes have elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, increased hemoglobin concentration, propensity to thrombosis and early mortality. Because the mutation persists from an ancient origin, we hypothesized that there is a heterozygote advant...

von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that is associated with various tumors and cysts in the central nervous system (CNS) and other visceral organs. Inactivation of the VHL tumor suppressor protein with loss of function of the VHL protein, and Elongin B, C complex results in a dysfunction of the ubquitination of hypoxia-inducible factor, which is an important step i...

OBJECTIVE To determine the germline mutation in an extended family in which 1 member was diagnosed clinically with von Hippel-Lindau (VHL) disease and to investigate 3 generations of the family. SUBJECTS AND METHODS The polymerase chain reaction-single strand conformation polymorphism sequencing techniques were used to identify the germline mutation in the VHL gene in the patient and also to ...

The von Hippel-Lindau tumor-suppressor gene (VHL) is lost in most clear cell renal cell carcinomas (ccRCC). Here, using human ccRCC specimens, VHL-deficient cells, and xenograft models, we show that miR-204 is a VHL-regulated tumor suppressor acting by inhibiting macroautophagy, with MAP1LC3B (LC3B) as a direct and functional target. Of note, higher tumor grade of human ccRCC was correlated wit...

The mechanisms by which molecular chaperones assist quality control of cytosolic proteins are poorly understood. Analysis of the chaperone requirements for degradation of misfolded variants of a cytosolic protein, the VHL tumor suppressor, reveals that distinct chaperone pathways mediate its folding and quality control. While both folding and degradation of VHL require Hsp70, the chaperonin TRi...