Von Hippel-Lindau Vignette Flashcards Preview

M2M Unit III > Von Hippel-Lindau Vignette > Flashcards

Flashcards in Von Hippel-Lindau Vignette Deck (11):
1

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

2

Molecular Basis

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)

3

ccRCC

In VHL, see many cysts on bilateral kidneys, highly vascularized tumors. Many cysts due to inherited loss of one copy.

4

ccRCC Treatment

surgical resection with partial nephrectomy. Metastatic tumors treated with VEGF-R TKIs, mTOR inhibitors, and immunotherapies against HIF proteins.

5

Hemangioblastoma

Highly vascularized tumor

6

VHL Type 1

Hemangioblastoma & ccRCC
total/partial loss of VHL gene

7

VHL Type 2a

Hemangioblastoma & Phenochromocytoma
VHL missense mutation, HIF up-regulation

8

VHL Type 2b

Hemangioblastoma & Phenochromocytoma & ccRCC
VHL missense, HIF up-regulation

9

VHL Type 2c

Phenochromocytoma only
VHL Missense

10

VHL Gene Location/Function

Chromosome 3p25-26

Targets proteins for proteasomal degradation

11

Sorafenib and Sunitinib

TKIs for VEGFRs and PDGFRs