胃肠间质瘤基因突变和分子靶向治疗相关研究进展

胃肠管间质瘤是最常见的胃肠管原发的间叶源性肿瘤.胃肠管间质瘤的发生是由KIT基因突变导致KIT蛋白的组成性激活引起的.血小板源性生长因子受体α(platelet-derived growth factor receptor alpha,PDGFRA)也与胃肠管间质瘤的发病机制有关.KIT的突变位点主要是exon11、exon9、exon13和exon17;PDGFRA的突变位点主要是exon18、exon12和exon14.胃肠间质瘤的临床病理参数、对甲磺酸依马替尼的反应与突变所在的位置及突变类型相关.甲磺酸伊马替尼是一个选择性的小分子酪氨酸激酶抑制剂,其临床应用是胃肠管间质瘤分子靶向治疗的里程碑.本文就胃肠管间质瘤基因突变和分子靶向治疗的研究进展概述.

Gene mutation and targeted therapy development of gastrointestinal stromal tumors

Gastrointestinal stromal tumors are the common mesenchymal tumors of the gastrointestinal tract. The constitutive activation of KIT is one of the earlies ttransforming events in GISTs and occurs mainly through activating mutations in the kit gene. PDGFRa is associated with the pathogenesis of GISTs too. The main mutative site of KIT gene are exon11, exon9, exon13 and exon17 and those of PDGFRA are exon18, exon12 and exon14.The clinical parameter and the response to imatinib of GISTs are associated with the site and type of gene mutation. Imatinib mesylate is a small-molecule inhibitor that selectively inhibit the tyrosine kinase and the clinical use of it is one milestone of the targeted therapy of GISTs. We review the gene mutation and targeted therapy development of gastrointestinal stromal tumors in this article.