Vascular Anomalies: From a Clinicohistologic to a Genetic Framework.
Vascular Anomalies: From a Clinicohistologic to a Genetic Framework.
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DOI：
10.1097/prs.0000000000004294
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发表时间：
2018-05
影响因子：
3.6
通讯作者：
Goss JA
中科院分区：
文献类型：
--
作者：
Greene AK;Goss JA
目前，血管异常根据其临床和组织学特征进行分类。分子遗传学的最新进展使得在大多数类型的血管异常中识别体细胞突变成为可能。本研究的目的是整理有关血管异常的遗传基础的信息。对PubMed文献中1994-2017年期间发现血管异常突变的所有引文进行了审查。检索词包括“血管异常”、“突变”、“基因”、“血管瘤”、“化脓性肉芽肿”、“卡波西样血管内皮瘤”、“毛细血管畸形”、“静脉畸形”、“淋巴管畸形”、“动静脉畸形”和“综合征”。分析了在血管畸形中识别生殖系和体细胞突变的文章。突变按类型（种系或体细胞）、基因、信号传导途径和突变富集细胞分类。大多数血管异常具有通常通过RAS或PIK 3CA途径影响酪氨酸激酶受体信号传导的相关突变。PIK 3CA和G蛋白偶联受体中的突变最常被鉴定。特定类型的血管异常通常与单个基因相关。但在不同的血管病变中，偶尔也会发现同一基因的突变，有些异常有一个>1个基因的突变。突变最常见于内皮细胞。在血管异常中识别体细胞突变正在改变诊断和理解病变的范式。突变及其通路为开发新的药物治疗提供了潜在的靶点。在未来，血管异常将根据临床特征以及分子病理生理学进行管理。
Vascular anomalies currently are classified according to their clinical and histological characteristics. Recent advances in molecular genetics have enabled the identification of somatic mutations in most types of vascular anomalies. The purpose of this study was to collate information regarding the genetic basis of vascular anomalies. The PubMed literature was reviewed for all citations that identified a mutation in a vascular anomaly between 1994–2017. Search words included “vascular anomaly”, “mutation”, “gene”, “hemangioma”, “pyogenic granuloma”, “kaposiform hemangioendothelioma”, “capillary malformation”, “venous malformation”, lymphatic malformation”, “arteriovenous malformation”, and “syndrome”. Articles that identified both germline as well as somatic mutations in vascular anomalies were analyzed. Mutations were categorized by type (germline or somatic), gene, signaling pathway, and cell(s) enriched for the mutation. The majority of vascular anomalies had associated mutations that commonly affected tyrosine kinase receptor signaling through the RAS or PIK3CA pathways. Mutations in PIK3CA and G-protein coupled receptors were most frequently identified. Specific types of vascular anomalies usually were associated with a single gene. However, mutations in the same gene occasionally were found in different vascular lesions, and some anomalies had a mutation in >1 gene. Mutations were most commonly enriched in endothelial cells. Identification of somatic mutations in vascular anomalies is changing the paradigm by which lesions are diagnosed and understood. Mutations and their pathways are providing potential targets for the development of novel pharmacotherapy. In the future, vascular anomalies will be managed based on clinical characteristics as well as molecular pathophysiology.