scholarly journals Primary Clear Cell Microcystic Adenoma of the Sinonasal Cavity: Pathological or Fortuitous Association?

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Rosalin Cooper ◽  
Hannah Markham ◽  
Jeffery Theaker ◽  
Adrian Bateman ◽  
David Bunyan ◽  
...  
Keyword(s):  
Clear Cell ◽  
Surgical Excision ◽  
Loss Of Function ◽  
Cancer Syndrome ◽  
Cell Renal Cell Carcinoma ◽  
Inherited Cancer ◽  
Von Hippel Lindau ◽  
Microcystic Adenoma ◽  
Vhl Disease ◽  
Inherited Cancer Syndrome

Primary clear cell microcystic adenoma of the sinonasal cavity is rare. It has previously been described only as a VHL-associated tumour. Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome characterised by an elevated risk of neoplasia including clear cell renal cell carcinoma (ccRCC), haemangioblastoma, and phaeochromocytoma. We describe the second reported case of a primary clear cell microcystic adenoma of the sinonasal cavity. The 39-year-old patient with VHL syndrome had previously undergone resection and ablation of ccRCC. He presented with epistaxis. Imaging demonstrated a mass in the ethmoid sinus. Initial clinical suspicion was of metastatic ccRCC. However, tumour morphology and immunoprofile were distinct from the previous ccRCC and supported a diagnosis of primary microcystic adenoma. Analysis of DNA extracted from sinonasal tumour tissue did not show loss of the wild-type allele at the VHL locus. Although this did not support tumour association with VHL disease, it was not possible to look for a loss-of-function mutation. The association of primary microcystic adenoma of the sinonasal cavity with VHL disease remains speculative. These lesions are benign but are likely to require regular surveillance. Such tumours may require repeated surgical excision.

scholarly journals Von Hippel-Lindau disease and endocrine tumour susceptibility

2006 ◽  
Vol 13 (2) ◽  
pp. 415-425 ◽  
Author(s):  
Emma R Woodward ◽  
Eamonn R Maher
Keyword(s):  
Target Genes ◽  
Phenotypic Variability ◽  
Familial Cancer ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Cancer Syndrome ◽  
Pancreatic Islet Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Vhl Disease

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by mutations in the VHL tumour suppressor gene. VHL disease is characterised by marked phenotypic variability and the most common tumours are haemangioblastomas of the retina and central nervous system and clear cell renal cell carcinoma. However, endocrine tumours, most commonly phaeochromocytoma and non-secretory pancreatic islet cell cancers, demonstrate marked interfamilial variations in frequency and are significant causes of morbidity and, sometimes, mortality. Genotype–phenotype correlations have revealed that certain missense mutations are associated with a high risk of phaeochromocytoma but total loss of function mutations are associated with a low risk. Furthermore, rare mutations may predispose to a phaeochromocytoma-only phenotype. Germline VHL mutations may be detected in 5–11% of all phaeochromocytoma cases and mutation analysis of VHL and other phaeochromocytoma susceptibility genes (SDHB, SDHD and RET) should be performed in all cases of familial, multiple or early onset phaeochromocytomas, and considered in other cases. The VHL gene product has a key role in regulating the stability of hypoxia-inducible factors (HIF-1 and HIF-2) such that inactivation of VHL leads to up-regulation of HIF-1 and HIF-2 protein expression and activation of hypoxic gene response pathways. Germline SDHB and SDHD mutations also lead to increased expression of HIF target genes, but it appears that phaeochromocytoma susceptibility in VHL disease cannot be attributed to HIF activation alone. Recently, it has been suggested that an HIF-independent failure of developmental apoptosis is a common feature of all inherited phaeochromocytoma susceptibility syndromes.

Molecular pathology of von Hippel–Lindau disease and the VHL tumour suppressor gene

2001 ◽  
Vol 3 (8) ◽  
pp. 1-27 ◽  
Author(s):  
Frances M. Richards
Keyword(s):  
Hypoxia Inducible Factor ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Missense Mutations ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Von Hippel Lindau ◽  
Adrenal Chromaffin ◽  
Vhl Disease

von Hippel–Lindau (VHL) disease is a dominantly inherited cancer syndrome characterised by predisposition to multiple tumours of the eyes and central nervous system (haemangioblastomas), kidneys (renal cell carcinoma; RCC), adrenal chromaffin cells (phaeochromocytoma), and other organs. The VHL gene was isolated in 1993 and mutations or deletions in the VHL gene have been identified in the germline of nearly all tested individuals with VHL disease. Genotype–phenotype correlations have been observed: individuals with missense mutations are more likely to develop phaeochromocytoma than those with deletions or protein-truncating mutations are, and specific missense mutations at certain codons might not predispose to RCC. In accordance with its role as a tumour suppressor gene, the normal allele of the VHL gene is deleted, mutated or silenced by promoter methylation in the tumours from VHL patients, and in a large proportion of sporadic tumours of the same histological types as observed in VHL disease. Thus, the VHL gene is of major importance in the development of RCC in the general population. Recent advances in understanding the structure and function of the VHL protein (pVHL) have revealed insights into the different phenotypes, with indications that some retention of function might be required for predisposition to phaeochromocytoma. pVHL interacts with many cellular proteins, mainly via one of two protein-binding domains (α and β). The best-characterised interaction is that of pVHL with elongin C, which forms a complex with elongin B and Cullin 2 proteins. This complex has E3 ubiquitin ligase activity and promotes ubiquitin-mediated proteasomal degradation of the hypoxia-inducible factor 1α (HIF-1α) transcription factor under normal oxygen (normoxic) conditions. Loss of pVHL function leads to stabilisation of HIF-1 and expression under normoxic conditions of hypoxia-inducible genes including vascular endothelial growth factor (VEGF), which might explain the hypervascular phenotype of VHL tumours. Several other genes implicated in intra- and intercellular signalling and control of tumour growth are overexpressed in the absence of pVHL, but it is not yet clear which features of pVHL function are most significant for tumour suppression in different tissues. Further advances in understanding pVHL function might eventually enable development of specific therapies for prevention or treatment of VHL tumours and RCC.

Von Hippel–Lindau disease

2015 ◽  
Author(s):  
Thomas Connor ◽  
Patrick H. Maxwell
Keyword(s):  
Cellular Response ◽  
Familial Cancer ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Loss Of Function ◽  
Cancer Syndrome ◽  
Von Hippel Lindau ◽  
Vhl Disease

Von Hippel–Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by germline mutations in the VHL tumour suppressor gene. The most frequent manifestations of VHL disease are retinal and central nervous system haemangioblastomas, clear cell renal cell carcinomas, and phaeochromocytomas. Genetic testing and active screening for clinical manifestations is now started in childhood and has greatly improved the prognosis for patients with VHL disease. The VHL protein plays a critical role in regulating the cellular response to changes in oxygen tension. Loss of VHL function results in constitutive activation of a range of angiogenic and metabolic pathways. New drug therapies have been developed that reverse some of the cellular consequences of VHL loss of function in kidney cancer.

scholarly journals Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Ming-xiao Zhang ◽  
Li-zhen Zhang ◽  
Liang-min Fu ◽  
Hao-hua Yao ◽  
Lei Tan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Positive Feedback ◽  
Renal Cell ◽  
Clear Cell ◽  
Biological Significance ◽  
Specific Inhibitor ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma

AbstractLong noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

Sign in / Sign up

Export Citation Format

Share Document