c-kit和PDGFRA基因对胃肠间质瘤的影响

胃肠间质瘤(gastrointestinal stromal tumors,GIST)是较常见的人消化道间叶性肿瘤，多发于胃部.尽管有不同临床病理特征，但绝大多数GIST均存在c-kit或血小板衍生生长因子受体α(PDGFRA)基因突变. c-kit、PDGFRA的抑制剂—格列卫是目前主要应用于GIST治疗的分子靶向治疗药物，c-kit、PDGFRA的不同基因状态会对分子靶向治疗药物呈现不同的反应.c-kit基因外显子11发生突变的GIST对格列卫呈现良好的反应，而外显子 9突变对格列卫的反应略差.另外发现,c-kit、PDGFRA基因的二次突变会引起格列卫抗性.本文简要介绍c-kit、 PDGFRA基因与GIST的临床表现、分子靶向治疗之间的关系及其二次突变的特征.

Mutation of c-kit and PDGFRA Genes in Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors are the most common type of sarcoma arising in the digestive tract, being commonly found in the stomach. Despite clinicopathological differences, most of the GISTs share oncogenic c-kit or platelet-derived growth factor-α(PDGFRA) mutations.Imatinib, c-kit and PDGFRA inhibitor, being successfully used in the treatment of GISTs and the response to the targeted treatment depend on the c-kit or PDGFRA mutation status. c-kit exon 11 mutants respond well to imatinib，while exon 9 mutants are less sensitive.GISTs withc-kit or PDGFRA secondary mutations will be resistant to imatinib. In this review, the correlation between c-kit and PDGFRA genes and clinical manifestation,molecular targeted therapy of GIST and the secondary c-kit and PDGFRA mutations will be elucidated.