肝转移胃肠道间质瘤c—kit、PDGFRA基因突变研究

Liver metastases from gastrointestinal stromal tumors： c-kit and PDGFRA mutational analysis

目的探讨肝转移胃肠道间质瘤（GIST）发生的机制。方法应用聚合酶链反应（PCR）和基因测序法检测12例肝转移GISTc—kit基因第9、11、13、17号外显子和PDGFRA第12、18号外显子序列，总结基因突变规律，分析其与临床病理的关系。结果本组5例胃部，1例小肠，其他6例。本组c—kit基因突变率为91．7％（11／12），外显子11为83．3％（10／12）。未检测到PDG—FRA基因突变。本组性别、年龄、原发部位、肿瘤大小、核分裂相、NIH危险度分级、肝转移时间、细胞形态、细胞丰富程度、核异型对c—kit基因外显子11突变率及突变形式影响差异无统计学意义（P〈0．05）。结论肝转移GIST基因突变主要集中在c．kit第11号外显子。突变方式有缺失、点突变和缺失伴点突变。缺失突变多见。肝转移GIST临床病理与外显子11突变率、突变形式无明显相关。

Objective To investigate the mechanisms of liver metastases from gastrointestinal stromal tumors （GISTs）. Methods Twelve patients with liver metastases from GIST were studied. Exons 9, 11, 13, and 17 of c-kit gene as well as exon 12 and exon 18 of PDGFRA gene were sequenced. Results There were 5 cases of GISTs in stomach, 1 in small intestine and 6 in others. The c-kit and exon 11 mutation rate was 91.7% and 83.3% , respectively. There was no correlations between sex, age, primary loca-tion, size, nucler mitose, NIH risk classification, liver metastases time, morphology, cellularity, nuclear- atypia with c-kit exon 11 mutation rate and mutation forms. Conclusion The mutation of liver metastases from GISTs is mainly located in c-kit exon 11. The mutation forms are deletion, point and deletion plus point. There is no obvious correlation between c-kit exon 11 mutation rate, mutation forms and chnicopath- ological features of liver metastases from GISTs.