Flashcards in Von Hippel-Lindau Vignette Deck (11):
VHL Clinical Manifestations
Cystic, highly vascularized tumors: spinal cord, cerebellum, renal hemangioblastomas. Bilateral kidney cysts, ccRCC. Phenochromocytomas, panreatic cysts, etc
Diagnosed with 1 lesion and family history or 2 lesions with no history
Autosomal dominant inheritance of VHL (Chr3p25-26) mutation 1/36,000 births.
VHL in ubiquitin ligase complex, ubiquitinates HIF, suppresses aneuploidy, stabilizes microtubules.
After mutation, HIF activates TFs for PDGF, VEGF, and TGF a/b (angiogenesis, metabolism, apoptosis)
In VHL, see many cysts on bilateral kidneys, highly vascularized tumors. Many cysts due to inherited loss of one copy.
surgical resection with partial nephrectomy. Metastatic tumors treated with VEGF-R TKIs, mTOR inhibitors, and immunotherapies against HIF proteins.
Highly vascularized tumor
VHL Type 1
Hemangioblastoma & ccRCC
total/partial loss of VHL gene
VHL Type 2a
Hemangioblastoma & Phenochromocytoma
VHL missense mutation, HIF up-regulation
VHL Type 2b
Hemangioblastoma & Phenochromocytoma & ccRCC
VHL missense, HIF up-regulation
VHL Type 2c
VHL Gene Location/Function
Targets proteins for proteasomal degradation