Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations

Area of Science:

• Vascular biology
• Genetics
• Cell biology

Background:

• Somatic mutations in GNAQ (encoding Gαq) are present in capillary malformation tissue.
• The specific cell type harboring the GNAQ mutation in these malformations remains unidentified.

Purpose of the Study:

• To determine the precise cell type within capillary malformations that carries the GNAQ mutation.
• To investigate the cellular basis of GNAQ-related vascular anomalies.

Main Methods:

• Human capillary malformation tissues from 13 patients were analyzed.
• Droplet digital polymerase chain reaction (ddPCR) quantified GNAQ mutant allelic frequencies.
• Fluorescence-activated cell sorting (FACS) isolated cell populations (hematopoietic, endothelial, perivascular, stromal) for mutation analysis.

Main Results:

• GNAQ mutations (p.R183Q, p.R183L, p.R183G) were detected in 8 of 13 capillary malformations.
• Mutant allelic frequencies ranged from 2% to 11%.
• FACS analysis revealed GNAQ mutations specifically within endothelial cells, with mutant allelic frequencies from 3% to 43%, and not in platelet-derived growth factor receptor-β-positive cells.

Conclusions:

• Endothelial cells are significantly enriched for GNAQ mutations in capillary malformations.
• These GNAQ mutations in endothelial cells are the likely drivers of capillary malformation pathophysiology.