The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis

Hudler, Petra; Urbančič, Mojca

doi:10.3390/genes13020362

Cited by 22 publications

(11 citation statements)

References 192 publications

(301 reference statements)

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“…pVHL consists mainly of α domain and β domain. The α domain mainly forms a VCB-CUL2 complex with elongin B and elongin C, further constituting E3 ubiquitinase ( 36 ). The β domain mainly interacts with the hypoxia-inducible factor HIF-α ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

VHL syndrome without clear family history: A rare case report and literature review of Chinese patients

Xin²,

Song³

et al. 2022

Front. Neurol.

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ObjectiveTo analyze the clinical manifestations and imaging features of a hospitalized patient with intermittent headache who was finally diagnosed with von Hippel–Lindau (VHL) syndrome and to perform whole-exon gene detection to improve the understanding of the diagnosis and treatment strategies of the disease.MethodsA case of suspected VHL syndrome in Shanxi Provincial People's Hospital was analyzed. Proband DNA was also extracted for whole exome sequencing and screened for causative mutation sites, which were validated by Sanger sequencing. The literature about VHL gene mutations in Chinese patients in the past 10 years were also reviewed.ResultsThere is a heterozygous mutation site c.499C > G on the VHL gene on the short arm of chromosome 3 of the patient, which is a missense mutation. The mutation results in the substitution of arginine with glycine at amino acid 167 of the encoded protein, which may be primarily responsible for the disease in the patient with VHL syndrome. However, the mutation did not occur in other family members.ConclusionEarly recognition and treatment of VHL syndrome can be available with genetic testing technology. Strengthening the understanding of this complex genetic disease and improving the diagnostic rate of VHL syndrome are helpful for the precise treatment of patients with this disease, which may help prolong the survival time of patients to a certain extent and improve their quality of life.

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Section: Discussionmentioning

confidence: 99%

VHL syndrome without clear family history: A rare case report and literature review of Chinese patients

Xin²,

Song³

et al. 2022

Front. Neurol.

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“…The significant association between hemangioblastoma and polycythemia is well documented [28,29]. The alteration of the VHL tumor suppressor gene results in the stabilization of hypoxia-induced factor 1/2α, which then increases the biosynthesis of erythropoietin (EPO), and thus leads to polycythemia [30].…”

Section: Indications Provided By Haematocrit Level Analysismentioning

confidence: 99%

Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up

Garrido,

Ngoc,

Guyotat

et al. 2024

Cancers

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The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were retrospectively analyzed. The mean age at diagnosis was of 48 ± 16 years. Eleven (14%) patients had von Hippel–Lindau disease. The most frequent tumor location was the cerebellar hemispheres (n = 51, 65%) and 11 (14%) patients had multicentric hemangioblastomas. A gross total resection was achieved in 75 (93%) patients. Eighteen (22%) patients had a local progression, with a median progression-free survival of 56 months 95% CI [1;240]. Eleven (14%) patients had a distant progression (new hemangioblastoma and/or growth of an already known hemangioblastoma). Local progression was more frequent in younger patients (39 ± 14 years vs. 51 ± 16 years; p = 0.005), and those with von Hippel–Lindau disease (n = 8, 44% vs. n = 3, 5%, p < 0.0001), multiple cerebral locations (n = 3, 17% vs. n = 2, 3%, p = 0.02), and partial tumoral resection (n = 4, 18% vs. n = 1, 2%, p = 0.0006). Therefore, it is advisable to propose a postoperative follow-up for at least 10 years, and longer if at least one predictor of progression is present.

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“…As pVHL has multiple functional domains, one of the potential explanations for this phenomenon is that a specific mutation causes a particular dysfunction. Specifically, mutations in the VHL gene on chromosome 3 affect the functionality of pVHL, i.e., as pVHL is incapable of recognizing hydroxylated HIFs, their greater stability leads to HIF-mediated transcription of genes and consequent development of VHL disease ( Figure 1 ) ( 71 , 72 ). The role of VHL in disease development has been described in detail elsewhere by Hudler and colleagues ( 71 ).…”

Section: Hypoxia Inducible Factors: Overview Of Structure Function An...mentioning

confidence: 99%

“…Nonetheless, other HIF-independent proteins and pathways can also be dysregulated in VHL-mutated tumors, e.g., the developmental neuronal apoptosis pathway, p53-related networks, and glucose metabolism. Likewise, the HIF-independent defective apoptosis pathway (for example in type 2C VHL disease) cannot induce apoptosis in chromaffin cells due to greater stability of p53 ( 85 ), and some of the type 2C mutations interfere with the regulation of transcription factor AP-1 (JUN)-induced apoptosis due to a VHL-mediated reduction in Jun-B and EGLN3 / PHD3 levels ( 71 , 86 , 87 ).…”

Section: Hypoxia Inducible Factors: Overview Of Structure Function An...mentioning

confidence: 99%

Hypoxia signaling pathway: A central mediator in endocrine tumors

et al. 2023

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Adequate oxygen levels are essential for the functioning and maintenance of biological processes in virtually every cell, albeit based on specific need. Thus, any change in oxygen pressure leads to modulated activation of the hypoxia pathway, which affects numerous physiological and pathological processes, including hematopoiesis, inflammation, and tumor development. The Hypoxia Inducible Factors (HIFs) are essential transcription factors and the driving force of the hypoxia pathway; whereas, their inhibitors, HIF prolyl hydroxylase domain (PHDs) proteins are the true oxygen sensors that critically regulate this response. Recently, we and others have described the central role of the PHD/HIF axis in various compartments of the adrenal gland and its potential influence in associated tumors, including pheochromocytomas and paragangliomas. Here, we provide an overview of the most recent findings on the hypoxia signaling pathway in vivo, including its role in the endocrine system, especially in adrenal tumors.

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The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis

Cited by 22 publications

References 192 publications

VHL syndrome without clear family history: A rare case report and literature review of Chinese patients

VHL syndrome without clear family history: A rare case report and literature review of Chinese patients

Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up

Hypoxia signaling pathway: A central mediator in endocrine tumors

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