The von Hippel-Lindau tumor suppressor gene

Decker, H.J.; Weidt, Eberhardt; Brieger, Juergen

doi:10.1016/s0165-4608(96)00296-8

Cited by 55 publications

(4 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular genetic alterations underlying the growth of haemangioblastomas were poorly understood until recently and it was not clear if one or both types of tumour cells (stromal and endothelial) are neoplastic. Loss of heterozygosity (LOH) at the VHL locus has been demonstrated both in sporadic and VHL‐related haemangioblastomas (review in [ 17]). Moreover, point mutation and deletions of the VHL gene have been documented in haemangioblastoma and may represent a significant event in the development of these tumours [ 17–20].…”

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

“…Loss of heterozygosity (LOH) at the VHL locus has been demonstrated both in sporadic and VHL‐related haemangioblastomas (review in [ 17]). Moreover, point mutation and deletions of the VHL gene have been documented in haemangioblastoma and may represent a significant event in the development of these tumours [ 17–20]. More recently, hypermethylation of the VHL gene has been reported for the first time as another mechanism of VHL gene inactivation in VHL‐related CNS haemangioblastomas [ 21].…”

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

“…It is also of great interest in view of the direct implication of the VHL gene in regulation of VEGF and angiogenesis, besides its interaction with elongin [ 25, 26]. The VHL gene regulates VEGF expression, maybe at a post‐transcriptional level, and the VHL gene inactivation causes a loss of VEGF suppression leading to proliferation of blood capillaries [ 17, 26–28]. On the other hand, the exact cellular origin of erythropoietin, responsible for the classic polycythaemia secondary to cerebellar haemangioblastoma (occurring in about 20% of cases), is not yet elucidated.…”

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

See 2 more Smart Citations

Haemangioblastoma of the central nervous system in von Hippel–Lindau disease

Richard

Campello

Taillandier

et al. 1998

Journal of Internal Medicine

187

115

View full text Add to dashboard Cite

Haemangioblastoma of the central nervous system (CNS) is the most characteristic lesion and the most common presenting manifestation of von Hippel-Lindau (VHL) disease and has a striking tendency to multiple occurrence. Its sites of predilection are the posterior fossa (cerebellum++), and the spinal cord. Haemangioblastoma may cause increased intracranial pressure and/or neurological deficits and remains the main cause of morbidity and mortality in VHL. Treatment of symptomatic haemangioblastoma remains neurosurgical and is often in emergency. Haemangioblastoma appears to be more commonly associated with VHL than previously reported and suggests that all patients with 'sporadic' haemangioblastoma should be investigated for evidence of VHL disease. From a fundamental point of view, haemangioblastoma is a benign neoplastic entity with a double, vascular and cellular differentiation. Mutational inactivation of both copies of the VHL gene plays a major role in the pathogenesis of haemangioblastoma. Over-expression of vascular endothelial growth factor (VEGF) and VEGF-receptors has been recently demonstrated in these tumours, raising the possibility of angioblastic origin, and is of very great interest in view of the direct implication of the VHL gene in negative regulation of VEGF.

show abstract

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

Section: Recent Advances In Haemangioblastoma Pathogenesismentioning

confidence: 99%

See 1 more Smart Citation

Haemangioblastoma of the central nervous system in von Hippel–Lindau disease

Richard

Campello

Taillandier

et al. 1998

Journal of Internal Medicine

187

115

View full text Add to dashboard Cite

show abstract

“…Von Hippel–Lindau (VHL) disease is an autosomal dominant inherited familial cancer syndrome predisposing to retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and renal cysts, phaeochromocytoma and pancreatic cysts and tumours, epididymal cysts and endolymphatic sac tumours [ 1, 2]. The birth incidence of VHL disease is thought to be one in 36 000 per year [ 3] with an estimated de novo mutation rate of 4.4 × 10 −6 gametes per generation [ 3, 4].…”

Section: Introductionmentioning

confidence: 99%

Molecular genetic analysis of von Hippel–Lindau disease

Richards

Webster²,

McMahon

et al. 1998

Journal of Internal Medicine

View full text Add to dashboard Cite

Richards FM, Webster AR, McMahon R, Woodward ER, Rose S, Maher ER (Birmingham University; Birmingham Women's Hospital, Birmingham; Addenbrooke's Hospital, Cambridge; Cambridge University, Cambridge, UK). Molecular genetic analysis of von Hippel–Lindau disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 527–33. Von Hippel–Lindau (VHL) disease is a dominantly inherited multisystem family cancer syndrome predisposing to retinal and central nervous system haemangioblastomas, renal carcinoma, phaeochromocytoma, pancreatic islet cell tumours and endolymphatic sac tumours. In addition, renal, pancreatic and epididymal cysts occur. Morbidity and mortality from VHL disease can be reduced by the identification and surveillance of affected individuals and at‐risk relatives so that compli‐cations are diagnosed at an early presymptomatic stage. The detailed mapping and subsequent isolation of the VHL tumour suppressor gene has enabled molecular genetic analysis in families and patients with definite or possible VHL disease. Initially, linked DNA markers were used in informative families to modify individual risks and then to make appropriate alterations in surveillance programs. However, currently most DNA analysis involves the characterisation of germline mutations. World‐wide, mutations have been identified in almost 500 families (including 132 in our laboratory). These studies have revealed considerable heterogeneity both in the type and in the location of mutations within the VHL gene. In our experience, most recurrent mutations result from de novo mutations at hypermutable sequences, although a founder effect for the Tyr98His ("Black Forest') mutation has been reported in German and American families. Although many mutations are predicted to impair the ability of pVHL to combine with the elongin regulatory subunits, analysis of genotype–phenotype relationships suggests that the VHL protein has multiple and tissue specific functions. Calculation of tumour risks for different classes of VHL mutations has provided important prognostic information especially with respect to the likelihood of phaeochromocytoma. However, there is evidence that retinal involvement does not correlate with allelic heterogeneity, but that the variability in retinal angiomatosis is influenced by modifier gene effects. VHL gene mutation analysis also provides a basis for investigating the genetic basis of familial phaeochromocytoma and renal cell carcinoma, and apparently isolated retinal angiomas. Results to date suggest that a substantial proportion of patients with familial pheochromocytoma have VHL gene mutations but in contrast, most familial clusters of clear cell renal cell carcinoma (RCC) without evidence of VHL do not have germline VHL mutations.

show abstract

VHL Gene Deletion and Enhanced VEGF Gene Expression Detected in the Stromal Cells of Retinal Angioma

Chan

Vortmeyer²,

Chew³

et al. 1999

Arch Ophthalmol

125

View full text Add to dashboard Cite

Retinal angioma frequently occurs in von Hippel-Lindau (VHL) disease. However, VHL gene alterations have not been documented in retinal angiomas. Methods: Using tissue microdissection and polymerase chain reaction amplification, we have analyzed 7 retinal angiomas associated with VHL disease for loss of heterozygosity of the VHL gene. In addition, vascular endothelial growth factor expression was evaluated in these tumors by immunohistochemistry and in situ hybridization. Results: All 6 informative retinal angiomas showed loss of heterozygosity of the VHL gene. Loss of heterozygosity was detected in vacuolated "stromal" cells, but not in vascular cells or reactive glial tissue. Vascular endothelial growth factor protein and messenger RNA were also present in vacuolated "stromal" cells. Conclusions: These findings suggest that vacuolated "stromal" cells represent the true neoplastic component in retinal angioma. These cells express vascular endothelial growth factor and therefore may be responsible for abundant neovascularization of retinal angioma.

show abstract

The von Hippel-Lindau tumor suppressor gene

Cited by 55 publications

References 81 publications

Haemangioblastoma of the central nervous system in von Hippel–Lindau disease

Haemangioblastoma of the central nervous system in von Hippel–Lindau disease

Molecular genetic analysis of von Hippel–Lindau disease

VHL Gene Deletion and Enhanced VEGF Gene Expression Detected in the Stromal Cells of Retinal Angioma

Contact Info

Product

Resources

About