Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations.

Abstract:

BACKGROUND:A somatic mutation in GNAQ (c.548G>A; p.R183Q), encoding Gαq, has been found in syndromic and sporadic capillary malformation tissue. However, the specific cell type containing the mutation is unknown. The purpose of this study was to determine which cells in capillary malformations have the GNAQ mutation. METHODS:Human capillary malformation tissue was obtained from 13 patients during a clinically indicated procedure. Droplet digital polymerase chain reaction, capable of detecting mutant allelic frequencies as low as 0.1 percent, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence-activated cell sorting into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by droplet digital polymerase chain reaction. RESULTS:Eight capillary malformations contained GNAQ p.R183Q mutant cells, two lesions had novel GNAQ mutations (p.R183L and p.R183G), and three capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2 to 11 percent. Following fluorescence-activated cell sorting, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-β-positive cell population; mutant allelic frequencies were 3 to 43 percent. CONCLUSION:Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation.

journal_name

Plast Reconstr Surg

authors

Couto JA,Huang L,Vivero MP,Kamitaki N,Maclellan RA,Mulliken JB,Bischoff J,Warman ML,Greene AK

doi

10.1097/PRS.0000000000001868

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

77e-82e

issue

1

eissn

0032-1052

issn

1529-4242

pii

00006534-201601000-00029

journal_volume

137

pub_type

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