Cerebellar hemangioblastoma (Cerebellar hemangioblastoma) - Gen VHL
Hemangioblastoma is a tumor that develops in the newly formed blood vessels and tends to develop in the cerebellum and spinal cord, so it was known as cerebellar hemangioblastoma. Hemangioblastoma represents approximately 2% of intracranial tumors, arise most frequently in the cerebellar vermis and hemispheres. Histologically, the tumors are composed of multiple capillary and sinusoidal channels coated endothelial cells and lipid - laden groups pseudoxanthoma cells. Although usually a single tumor develops, multiple tumors may develop and also located in the brain stem, spinal cord, retina, and supratentorial compartment. Cerebellar hemangioblastoma usually develop in the third decade with intracranial hypertension, and ataxia.
This tumor, the tumor is most frequently associated with von Hippel-Lindau syndrome and is the leading cause of death, despite being benign and slow growing, since it is not always possible to access it through surgery. As the diagnosis is delayed, access is more difficult and the risk of surgery is greater.
When these tumors develop in people without von Hippel-Lindau syndrome, they are associated with somatic mutations in the VHL gene, located on the short arm of chromosome 3 (3p25.3). This gene encodes a protein that acts as part of a complex called VCB-CUL2. This complex drives other proteins to be degraded by the cell when no longer needed. One objective VCB-CUL2 complex of a protein called hypoxia inducible factor 2 alpha (HIF-2?). HIF-2? is a subunit of HIF complex that plays a critical role in oxygen homeostasis. HIF controls several genes involved in cell division, formation of new blood vessels, and the production of erythrocytes. Furthermore, it is the main regulator of the hormone erythropoietin, which controls the production of erythrocytes. HIF complex function is particularly important when oxygen levels are lower than normal (hypoxia). However, when adequate oxygen is available, VCB-CUL2 the complex makes HIF accumulates inappropriately in cells. The VHL protein probably plays a role in other cellular functions, including regulation of other genes and control cell division. Based on this function, the VHL protein is classified as a tumor suppressor, which means that prevents cells from growing and dividing too quickly or uncontrolled. The VHL protein is also involved in the formation of the extracellular matrix that provides structural support to tissue.
Mutations in the VHL gene result in an altered protein pVHL and therefore non - functional. Inactivation pVHL protein as a result of mutations in the sequence coding causes alteration of these processes and induces cells to grow and divide abnormally, which may contribute to tumor development.
Somatic mutations associated with hemangioblastomas occur during the life of a person and are present only in cells that give rise to blood and blood vessels.
Tests in IVAMI: in IVAMI perform detection of mutations associated with cerebellar hemangioblastoma, by complete PCR amplification of the exons of the VHL gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).