Clinical and functional properties of novel
            <i>VHL</i>
            mutation (X214L) consistent with Type 2A phenotype and low risk of renal cell carcinoma

Sorrell, AD; Lee, S; Stolle, Catherine A.; Ellenhorn, Joshua D. I.; Grix, Arthur; Kaelin, WG; Weitzel, JN

doi:10.1111/j.1399-0004.2010.01464.x

Cited by 9 publications

(9 citation statements)

References 24 publications

(37 reference statements)

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“…The VHL gene is originally known for causing von Hippel-Lindau disease, a rare autosomal dominant cancer syndrome, responsible for the appearance of incapacitating and life-threatening tumors in children and adults [Sorrell et al, 2011]. This disorder, caused by VHL germline mutations, includes tumors such as central nervous system hemangioblastoma, clear-cell renal cell carcinoma (RCC), PCC, and additional neuroendocrine tumors, endolymphatic sac tumors, cystadenomas in multiple locations, and renal and pancreatic cysts [Sorrell et al, 2011].…”

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

“…This disorder, caused by VHL germline mutations, includes tumors such as central nervous system hemangioblastoma, clear-cell renal cell carcinoma (RCC), PCC, and additional neuroendocrine tumors, endolymphatic sac tumors, cystadenomas in multiple locations, and renal and pancreatic cysts [Sorrell et al, 2011]. Depending on the specific VHL alteration, VHL disease has a considerable degree of heterogeneity, particularly in the age-related penetrance and in the types of tumors developed by the patients.…”

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

“…Depending on the specific VHL alteration, VHL disease has a considerable degree of heterogeneity, particularly in the age-related penetrance and in the types of tumors developed by the patients. Hence, genotype-phenotype correlations are crucial for predicting the risk of PCC: while VHL deletions or truncating mutations are associated with a high risk of RCC and low risk of PCC (VHL disease type 1), VHL missense mutations are linked to a higher risk of developing PCC (VHL disease type 2) [Favier et al, 2009;Sorrell et al, 2011;Ladroue et al, 2012;Lanikova et al, 2013]. Besides the cases associated with familial cancer syndromes, sporadic PCC/PGL may also carry somatic VHL mutations [Dahia, 2014].…”

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

“…The VHL tumor suppressor gene, which codes for pVHL, is located on the short arm of chromosome 3 and is composed of 3 exons [Sorrell et al, 2011]. pVHL forms an E3 ubiquitin ligase complex with elongin B, elongin C, Rbx1, and Cul2, which is able to recognize and bind to prolyl-hydroxylated HIFα under normoxia conditions.…”

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

See 3 more Smart Citations

Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas

Amorim-Pires

Peixoto²,

Lima³

2016

Cytogenet Genome Res

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Pheochromocytomas (PCC) and sympathetic paragangliomas (PGL) are rare neuroendocrine tumors, which derive from chromaffin cells occurring in the adrenal medulla and extra-adrenal sympathetic paraganglia. PCC and PGL are often benign, catecholamine-producing tumors, responsible for a myriad of symptoms that may be potentially hazardous to the patient. In contrast, nonsecreting parasympathetic PGL, derived from chief cells, develop mainly in the head and neck region. Although PCC/PGL are more commonly sporadic tumors, germline mutations are present in up to 40% of the patients, ranking these tumors among those with the highest degree of heritability. PCC/PGL are associated with a variety of hereditary syndromes, comprising genetic alterations in RET, NF1, VHL, and SDHx genes, the last 2 being involved in regulating the hypoxia pathway. Additional hypoxia pathway-related genes have been recently associated with PCC/PGL development, namely EGLN1 and EPAS1. Thus, dysregulation of the hypoxia pathway seems to play a major role in PCC/PGL development, in particular through the stabilization of hypoxia-inducible factors and the appearance of a pseudohypoxia signature. This article is focused on reviewing the tumorigenic mechanisms resultant from VHL, SDHx, EGLN1, and EPAS1 mutations, as well as the associated tumors, namely PCC/PGL, and extra manifestations such as polycythemia. In the light of the recent discoveries, hypoxia pathway molecules appear as key players in PCC/PGL development.

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Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

Section: Angiogenesis In Pcc and Pglmentioning

confidence: 99%

See 2 more Smart Citations

Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas

Amorim-Pires

Peixoto²,

Lima³

2016

Cytogenet Genome Res

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“…Inactivation of the VHL tumor suppressor gene is an archetypical tumor-initiating event in clear cell RCC (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs), which have opposing effects on clear cell carcinogenesis [9,10]. VHL-HIF response maintains an epigenetically altered which is specific to metastatic ccRCC in VHL-deficient cells [11].…”

Section: Introductionmentioning

confidence: 99%

Microarray Profiling of Human Renal Cell Carcinoma: Identification for Potential Biomarkers and Critical Pathways

Li¹,

Zhu²,

Che³

et al. 2013

Kidney Blood Press Res

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Aims: The aim of this study was to screen several novel genes associated with renal cell carcinoma (RCC), and analyze the gene functions and signal pathways which were critical to RCCs with DNA microarray. Methods: The gene expression profile of GSE781 was downloaded from Gene Expression Omnibus database, including 9 RCC samples and 9 healthy controls. Compared with the control samples, differentially expressed genes (DEGs) of RCC was identified the by packages in R. The selected DEGs were further analyzed using bioinformatics methods. Gene ontology (GO) enrichment analysis was performed using Gene Set Analysis Toolkit and protein-protein interaction (PPI) network was constructed with prePPI. Then, pathway enrichment analysis to PPI network was performed using WebGestalt software. Results: A total of 429 DEGs were down-regulated and 418 DEGs were up-regulated in RCC samples compared to healthy controls. A total of 11 remarkable enhanced functions and 13 suppressed functions were identified. PPI nodes of high degrees, such as JAK2, IL8, BMPR2, FN1 and NCR1, were obtained. The DEGs were classified and significantly enriched in cytokine and cytokine receptor pathway. Conclusion: The hub genes we find from RCC samples are not only bio-markers, but also may provide the groundwork for a combination therapy approach for RCCs.

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Hereditäre Tumorsyndrome in der Neuropathologie

Mawrin

2017

Pathologe

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Neoplasms in the central (CNS) and peripheral nervous system (PNS) in hereditary tumor syndromes play an important role in the neuropathological diagnostics. The benign and malignant PNS and CNS tumors that occur in the frequent neurofibromatosis type 1 (NF1) and type 2 (NF2) often represent essential factors for the course of the disease in those affected. Furthermore, certain clinical constellations (e.g. bilateral schwannomas of the auditory nerve, schwannomas at a young age and multiple meningiomas) can be important indications for a previously undiagnosed hereditary tumor disease. Other tumors occur practically regularly in association with certain germline defects, e.g. subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis and dysplastic gangliocytoma of the cerebellum in Cowden's syndrome and can be indications in the diagnostics for an extended genetic counselling. This is not only important because many germline defects are based on new mutations, but also for the now established targeted therapy of certain tumors, e.g. inhibition of the mammalian target of rapamycin (mTOR) signaling pathway using temsirolimus for SEGA. Furthermore, knowledge about the possible constellations of genetic mosaics in hereditary tumor syndromes with the resulting (incomplete) syndrome manifestations is useful. This review article summarizes the most important hereditary tumor syndromes with involvement of the PNS and CNS.

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Clinical and functional properties of novel VHL mutation (X214L) consistent with Type 2A phenotype and low risk of renal cell carcinoma

Cited by 9 publications

References 24 publications

Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas

Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas

Microarray Profiling of Human Renal Cell Carcinoma: Identification for Potential Biomarkers and Critical Pathways

Hereditäre Tumorsyndrome in der Neuropathologie

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