Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations.
Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations.
复制标题
毛细血管畸形的内皮细胞富含体细胞 GNAQ 突变。
DOI：
10.1097/prs.0000000000001868
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发表时间：
2016-01
影响因子：
3.6
通讯作者：
Greene AK
中科院分区：
文献类型：
--
作者：
Couto JA;Huang L;Vivero MP;Kamitaki N;Maclellan RA;Mulliken JB;Bischoff J;Warman ML;Greene AK
在综合征性和散发性毛细血管畸形组织中发现编码 Gαq 的 GNAQ (c.548G>A;p.R183Q) 体细胞突变。然而，包含突变的特定细胞类型尚不清楚。本研究的目的是确定毛细血管畸形中的哪些细胞具有 GNAQ 突变。人类毛细血管畸形组织是在临床指示的手术中从 13 名患者身上获得的。液滴数字 PCR (ddPCR) 能够检测低至 0.1% 的突变等位基因频率，用于量化毛细血管畸形组织中 GNAQ 突变细胞的丰度。通过荧光激活细胞分选术 (FACS) 将六个样本分为造血细胞、内皮细胞、血管周围细胞和基质细胞。通过 ddPCR 定量这些群体中 GNAQ 突变细胞的频率。 8 个毛细血管畸形含有 GNAQ p.R183Q 突变细胞，2 个病变具有新的 GNAQ 突变（p.R183L；p.R183G），3 个毛细血管畸形没有可检测到的 GNAQ p.R183 突变。突变等位基因频率范围为 2% 至 11%。 FACS 后，在内皮细胞中发现了 GNAQ 突变，但在血小板衍生生长因子受体 β 阳性 (PDGFRβ) 细胞群中未发现 GNAQ 突变；突变等位基因频率为3%至43%。毛细血管畸形中的内皮细胞富含 GNAQ 突变，并且可能与毛细血管畸形的病理生理学有关。
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(s) containing the mutation is unknown. The purpose of this study was to determine which cell(s) in capillary malformations have the GNAQ mutation. Human capillary malformation tissue was obtained from 13 patients during a clinically-indicated procedure. Droplet digital PCR (ddPCR), capable of detecting mutant allelic frequencies as low as 0.1%, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence activated cell sorting (FACS) into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by ddPCR. Eight capillary malformations contained GNAQ p.R183Q mutant cells, 2 lesions had novel GNAQ mutations (p.R183L; p.R183G), and 3 capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2% to 11%. Following FACS, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-β-positive (PDGFRβ) cell population; mutant allelic frequencies were 3% to 43%. Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation.