In this case, the identification of the VHL mutation led to careful screening and detection of clinically occult central nervous system hemangioblastomas and pancreatic neuroendocrine tumours.
Von Hippel-Lindau (VHL) gene mutations induce neural tissue hemangioblastomas, as well as highly vascularized clear cell renal cell carcinomas (ccRCCs).
The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed.
Hemangioblastomas (HBs) are uncommon tumors characterized by the presence of inactivating alterations in the von Hippel-Lindau (VHL) gene in inherited cases and by infrequent somatic mutation in sporadic entities.
VHL promoter hypermethylation was detected only in sporadic HBs (33%), indicating that epigenetic suppression of VHL is a common mechanism in sporadic HBs.
Alterations in VHL gene are rarely observed in the more common features of human VHL-related tumors in animal models, and VHL heterozygous knockout (VHL+/-) mice do not develop HBs.
Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau (VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor.
This is especially so in phenotypically variable diseases, such as von Hippel-Lindau disease (vHL). vHL is caused by germline mutations in the VHL gene, which predispose to the development of multiple tumors such as central nervous system hemangioblastomas and renal cell carcinoma (RCC).
The patterning of the similar embryonic vasculogenesis is an increasing concern in HB-neovascularization, and the classic vascular endothelial growth factor (VEGF)-mediated angiogenesis driven by VHL loss-of-function from human endothelium have been questioned.
Genotype-phenotype correlation studies show that patients with a complete deletion mutation of the VHL gene, relative to participants with a missense or protein-truncating mutation, had better visual acuity and decreased tumorigenesis incidence of retinal hemangioblastomas.
The authors described a case of a patient with co-existing endolymphatic sac tumor (ELST) and hemangioblastoma in the posterior cranial fossa, which belonged to a subtype of Von Hippel-Lindau (VHL) disease confirmed by the test of VHL-gene.
Measures evaluated include: visual acuity, features of ocular VHL disease (presence, location, number, and extent of retinal capillary hemangioblastomas [RCHs]), germline mutation in the VHL gene, demographics (age, gender, age at onset of ocular disease), and patient characteristics (smoking status, body mass index).
von Hippel-Lindau disease anchored in germline mutations of the VHL gene is rare in the Norwegian population as opposed to clinical VHL disease, which appears to be relatively common in patients with apparently sporadic hemangioblastomas.
Loss of heterozygosity (LOH) within the VHL gene is detected in the stromal cells surrounding the capillary endothelial cells and admixed with glial cells in ocular hemangioblastomas.
Clusterin shows possible important functions in tumor suppression by the VHL gene product (pVHL) and the potential to be a novel biomarker in retinal hemangioblastoma associated VHL disease.