Abstract
Extracranial arteriovenous malformation (AVM) is most commonly caused by MAP2K1 mutations in the endothelial cell. The purpose of this study was to determine if local tissue overgrowth associated with AVM is caused by direct or indirect effects of the MAP2K1 mutation (i.e., cell-autonomous or cell-non autonomous). Because cartilage does not have blood vessels, we studied ear AVMs to determine if overgrown cartilage contained AVM-causing mutations. Cartilage was separated from its surrounding tissue and isolated by laser capture microdissection. Droplet digital PCR (ddPCR) was used to identify MAP2K1 mutations. MAP2K1 (p.K57N) variants were present in the tissue adjacent to the cartilage [mutant allele frequency (MAF) 6–8%], and were enriched in endothelial cells (MAF 51%) compared to non-endothelial cells (MAF 0%). MAP2K1 mutations were not identified in the overgrown cartilage, and thus local cartilage overgrowth likely results from the effects of adjacent mutant blood vessels (i.e., cell-non autonomous).
Highlights
Extracranial arteriovenous malformation (AVM) progresses over time and causes overgrowth of tissues, including skin, subcutis, muscle, cartilage, and bone[1,2]
We previously have shown that extracranial AVMs contain somatic MAP2K1 mutations that are only contained in endothelial cells[3]
Because AVMs involving the ear are associated with significant cartilage overgrowth[1] and cartilage does not contain vasculature[6], we studied this clinical scenario to gain insight into the pathophysiology of AVMs
Summary
The purpose of this study was to determine if local tissue overgrowth associated with AVM is caused by direct or indirect effects of the MAP2K1 mutation. The purpose of this study was to determine if tissue overgrowth associated with AVM is caused by direct or indirect effects of a MAP2K1 mutation
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have