胃肠道间质瘤分子学研究进展

Advances in Molecular Studies of Gastrointestinal Stromal Tumors

摘要: 胃肠道间质瘤(Gastrointestinal Stromal Tumors, GIST)是胃肠道最常见的间叶源性肿瘤，其主要发病机制是c-kit与血小板源性生长因子受体PDGFRA基因突变。甲磺酸伊马替尼(Imatinib Mesylate, IM)可改善晚期GIST患者的生存期。然而部分患者因对IM耐药导致治疗失败。分子学研究表明约10%~15%的GIST无c-kit与PDGFRA基因突变，被称为野生型GIST。野生型GIST包括：NF1相关性、BRAF突变型、K-RAS突变型、四重野生型及其他基因突变型(PIK3CA突变) GIST与无综合征相关性、Carney三联征相关性、Carney-Stratakis综合征相关性GIST。同时表观遗传改变作为新的作用机制参与GIST的发生，对GIST的表观遗传的调控成为新的治疗方法。本文对国内外GIST分子学研究进行概述，旨在进一步阐明GIST的发病机制，为制定精准的个体化治疗方案提供帮助。

Abstract: Gastrointestinal Stromal Tumors (GIST) are the most common mesenchymal tumors of gastrointes-tinal tract, and the main pathogenesis is c-kit and PDGFRA gene mutations. Imatinib mesylate (IM) improves survival in patients with advanced GIST. However, some patients failed due to drug re-sistance to IM. Molecular studies have shown that about 10 to 15 percent of GIST is free of c-kit and PDGFRA mutations, known as wild-type GIST. Wild type GIST includes: NF1 correlation, BRAF muta-tion, K-RAS mutation, quadruple wild type and other gene mutations (PIK3CA mutation) GIST and syndrome-free correlation, Carney triad correlation, and Carney-Stratakis syndrome correlation GIST. Meanwhile, epigenetic changes are involved in the pathogenesis of GIST as a new mechanism of action, and epigenetic regulation of GIST becomes a new treatment method. This paper summa-rizes the molecular studies of GIST at home and abroad, aiming to further clarify the pathogenesis of GIST and provide help for the development of accurate and individualized treatment plans.