先天性血管瘤的遗传学研究进展及潜在药物治疗靶点  

Congenital hemangioma:genetic pathogenesis and potential targeted therapy

作　　者：王逸姝 华晨[1] 林晓曦[1] Wang Yishu;Hua Chen;Lin Xiaoxi(Department of Plastic and Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University,School of Medicine,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院整复外科,200011

出　　处：《中华整形外科杂志》2021年第9期1057-1062,共6页Chinese Journal of Plastic Surgery

摘　　要：先天性血管瘤是一种良性的血管源性肿瘤,由相关的遗传学病因导致,可分为快速消退型、不消退型和部分消退型。3种亚型的临床表现与组织病理学特征各有异同。该文综述了先天性血管瘤的遗传学发病机制,并提出潜在的靶向治疗方向。回顾文献发现可能的突变位点为GNAQ/GNA11基因体细胞突变和MYH9基因新生种系突变,其中GNAQ/GNA11突变会导致第209位谷氨酰胺被替换,可通过RAS/MAPK/ERK和Hippo/YAP信号通路促进血管瘤的发生。因此,上述信号通路中的关键分子ERK/MEK和YAP在未来或可作为先天性血管瘤患者靶向治疗的潜在靶点,成为新的特异性治疗方式。Congenital hemangioma(CH),a benign vascular tumor,is divided into rapidly involuting congenital hemangioma(RICH),noninvoluting congenital hemangioma(NICH)and partially involuting congenital hemangioma(PICH).Similarities and differences of clinical manifestation and histopathology exist in the three major subgroups,in which genetic variations probably play a part.This article focuses on genetic pathogenesis and provides potential targeted therapies.Somatic activating mutations in GNAQ or GNA11 and damaging de novo germline mutations in MYH9 were identified.GNAQ/GNA11 mutation that alters glutamine at amino acid 209 contributes to the formation of CH via RAS/MAPK/ERK and Hippo/YAP signaling pathways.Thus,ERK/MEK or Hippo/YAP,the critical components of aforementioned pathways,might become the potential target of CH therapy to develop a more specific treatment.

关 键 词：先天性血管瘤 发病机制 遗传学 靶向治疗 

分 类 号：R732.2[医药卫生—肿瘤]