scholarly journals Genotype and phenotype correlation in von Hippel–Lindau disease based on alteration of the HIF-α binding site in VHL protein

2018 ◽  
Vol 20 (10) ◽  
pp. 1266-1273 ◽  
Author(s):  
Sheng-Jie Liu ◽  
Jiang-Yi Wang ◽  
Shuang-He Peng ◽  
Teng Li ◽  
Xiang-Hui Ning ◽  
...  
Keyword(s):  
Binding Site ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Vhl Protein ◽  
Von Hippel Lindau Disease

scholarly journals von Hippel-Lindau Disease: an Update

2019 ◽  
Vol 7 (4) ◽  
pp. 227-235 ◽  
Author(s):  
Eamonn R Maher ◽  
Richard N Sandford
Keyword(s):  
Natural History ◽  
Patient Outcomes ◽  
Molecular Characterisation ◽  
Von Hippel Lindau ◽  
Functional Characterisation ◽  
History Of ◽  
Vhl Protein ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease ◽  
Improve Patient

Abstract Purpose of Review In this review, we discuss the key molecular and clinical developments in VHL disease that have the potential to impact on the natural history of the disease and improve patient outcomes. Recent Findings Identifiable mutations in VHL underlie most cases of VHL and define clear genotype-phenotype correlations. Detailed clinical and molecular characterisation has allowed the implementation of lifelong screening programmes that have improved clinical outcomes. Functional characterisation of the VHL protein complex has revealed its role in oxygen sensing and the mechanisms of tumourigenesis that are now being exploited to develop novel therapies for VHL and renal cancer. Summary The molecular and cellular landscape of VHL-associated tumours is revealing new opportunities to modify the natural history of the disease and develop therapies. Drugs are now entering clinical trials and combined with improved clinical and molecular diagnosis, and lifelong surveillance programmes, further progress towards reducing the morbidity and mortality associated with VHL disease is anticipated.

scholarly journals The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2313
Author(s):  
Isabel de Rojas-P ◽  
Virginia Albiñana ◽  
Lyudmyla Taranets ◽  
Lucía Recio-Poveda ◽  
Angel M. Cuesta ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Vascular Diseases ◽  
Hereditary Disease ◽  
In Vitro Assays ◽  
Second Hit ◽  
Von Hippel Lindau ◽  
Vhl Protein ◽  
Von Hippel Lindau Disease

Von Hippel–Lindau disease (VHL) is a rare hereditary disease characterized by the predisposal to develop different types of highly vascularized tumors. VHL patients carry a VHL mutation that causes partial lack of functional VHL protein (pVHL) in all cells, and a total lack thereof in cells harboring a second hit mutation. Absence of pVHL generates a prolonged state of pseudo-hypoxia in the cell due to accumulation of hypoxia inducible factor, an important transcription factor regulating pro-tumorigenic genes. The work here presented focuses on characterizing the endothelium of VHL patients, by means of blood outgrowth endothelial cells (BOECs). Transcriptome analysis of VHL-derived BOECs, further supported by in vitro assays, shows that these cells are at a disadvantage, as evidenced by loss of cell adhesion capacity, angiogenesis defects, and immune response and oxidative metabolic gene downregulation, which induce oxidative stress. These results suggest that the endothelium of VHL patients is functionally compromised and more susceptible to tumor development. These findings contribute to shedding light on the vascular landscape of VHL patients preceding the second hit mutation in the VHL gene. This knowledge could be useful in searching for new therapies for these patients and other vascular diseases.

scholarly journals Clear cell chondrosarcoma in Von Hippel-Lindau disease

2019 ◽  
Vol 19 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Koen M. A. Dreijerink ◽  
Rachel S. van Leeuwaarde ◽  
Wenzel M. Hackeng ◽  
Rachel H. Giles ◽  
Wendy W. J. de Leng ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Clear Cell ◽  
Immunohistochemical Analysis ◽  
Tumor Grade ◽  
Suppressor Gene ◽  
Clear Cell Chondrosarcoma ◽  
Von Hippel Lindau ◽  
Vhl Protein ◽  
Von Hippel Lindau Disease ◽  
A Cell

Abstract A diagnosis of clear cell chondrosarcoma of the ulna was made in a patient with Von Hippel-Lindau disease (VHL). After surgery, genetic analysis of the tumor tissue showed loss of heterozygosity at the VHL gene locus. Immunohistochemical analysis confirmed loss of expression of the VHL protein in the tumor cells. In addition, abundant Cyclin D1 expression in the tumor was observed. Chondrosarcoma has been described before in a VHL patient and VHL protein expression has been correlated to tumor grade in a series of sporadic chondrosarcomas. In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of the VHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL.

Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation

2010 ◽  
Vol 9 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Israel Gomy ◽  
Greice Andreotti Molfetta ◽  
Ester de Andrade Barreto ◽  
Cristiane Ayres Ferreira ◽  
Dalila Luciola Zanette ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Von Hippel Lindau Disease

Familial tumour syndromes: von Hippel–Lindau disease

2017 ◽  
Author(s):  
Hiroshi Kanno ◽  
Joachim P. Steinbach
Keyword(s):  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Laboratory Data ◽  
Von Hippel Lindau ◽  
Vhl Protein ◽  
Von Hippel Lindau Disease ◽  
The Central Nervous System ◽  
Microsurgical Techniques ◽  
Vhl Disease ◽  
Hif Pathway

Von Hippel–Lindau (VHL) disease, an autosomal dominant familial tumour syndrome, is often associated with haemangioblastoma of the central nervous system. In the presence of oxygen, VHL protein serves to prevent the accumulation of hypoxia-inducible factor (HIF) protein by targeting it to the proteasomal pathway, while biallelic inactivation of the VHL gene blocks degradation of HIF and leads to constitutive activation of the HIF pathway although oxygen is present. HIF-target genes are involved in angiogenesis, proliferation, and metabolism enabling tumour growth. Haemangioblastoma is a highly vascularized, begin tumour commonly associated with a cyst, but it is linked with neurological morbidity and mortality based on its location and multiplicity. Haemangioblastoma in VHL is diagnosed according to symptoms and signs, past and family histories, laboratory data, neuroradiological findings, pathological findings, and genetic testing. Surgical treatment is usually the most recommended therapy for haemangioblastomas, and using well-defined microsurgical techniques, the majority can be resected safely.

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