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.
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.
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.
Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation.
From the Departments of Plastic and Oral Surgery, Surgery, and Orthopedic Surgery, Vascular Anomalies Center, Vascular Biology Program, and the Howard Hughes Medical Institute, Boston Children’s Hospital; and the Department of Genetics, Harvard Medical School.
Received for publication February 19, 2015; accepted August 20, 2015.
Mr. Couto and Dr. Huang are co–first authors.
Disclosure:None of the authors has a financial interest in any of the products or devices mentioned in this article.
This work was supported by THE PLASTIC SURGERY FOUNDATION
Arin K. Greene, M.D., M.M.Sc., Department of Plastic Surgery and Oral Surgery, Boston Children’s Hospital, 300 Longwood Avenue, Boston, Mass. 02115, firstname.lastname@example.org