摘要
目的探讨胃肠道间质瘤(gastrointestinal stomal tumors,GIST)中c-kit基因和PDGFRA基因的突变多态性。方法对93例GIST标本采用PCR扩增和基因测序的方法检测c-kit基因9、11、13、17号外显子和PDGFRA基因12、18号外显子序列。结果在93例GIST中共检测到c-kit基因突变64例(68.82%),其中11号外显子突变56例,占全部病例的60.22%(56/93);9号外显子突变4例,占全部病例的4.30%(4/93);13号外显子突变3例,占全部病例的3.23%(3/93);17号外显子突变1例,为与11号外显子共突变,占全部病例的1.08%(1/93)。11号外显子突变方式以缺失突变最常见,占55.36%(31/56),其次是点突变(26.79%,15/56)和插入突变(串联重复)(14.29%,8/56),再次是伴点突变的缺失突变(3.57%,2/56);突变绝大多数为杂合性突变,少数为纯合性突变。突变位点多集中在5'端的经典热点,其次为3'端的框内串联重复。PDGFRA基因突变共检测到4例,其中1例为与c-kit共突变,其余3例占无c-kit突变病例的10.34%(3/29),占CD117阴性病例的37.5%(3/8),且均为18号外显子突变。结论大部分GIST中存在c-kit或PDGFRA基因的突变,少部分病例存在c-kit基因不同外显子双突变或c-kit基因和PDGFRA基因双突变共存型,其基因突变分型能指导伊马替尼的肿瘤靶向治疗。
Objective To explore mutation polymorphism of c-kit gene and PDGFRA gene in gastrointestinal stomal tumors （GIST）. Methods The sequences of 9 ^th, 11 ,h , 13 ,h and 17^th exons in c-kit gene and 12＇h and 18^th ex- ons in PDGFRA gene in 93 samples of GIST were detected by PCR amplification and gene sequencing method. Results Of 93 samples of GIST, 64 samples （68.82%） of gene mutation were detected in c-kit gene, among which 56 samples were 11th exon, and the percentage accounted for 60.22% （56/93） ; 4 samples were 9＇h exon, and the percentage ac- counted for 4.30% （4/93） ; 3 samples were 13^th exon, and the percentage accounted for 3.23% （3/93） ; 1 sample was 17＇s cxon with 11th exon of collective mutation, and the percent accounted for 1.08% （1/93）. The common gene muta- tion ways in 11th exon were deletion mutation, and accounted for 55. 36% （31/56）, followed by point mutation （26.79% , 15/56） and insertion mutation （tandem repeat） （14.29% , 8/56） , and the last one was deletion mutation associated with point mutation （3.57% , 2/56） ; the majority of mutations were heterozygosity, and a small of mutations were homozygosity. Mutation loci focused more on classic hot area on the 5＂side, and followed by the 3＂side of the tandem repeats within the box. Four samples of gene mutation were detected in PDGFRA gene, of which 1 sample was collective mutation with c-kit gene, the other 3 samples without c-kit mutation accounted for 10.34% （3/29） of mutation cases, and 37.5% （3/8） of CD117 negative cases, and all mutations were found in exon 18. Conclusion Gene mutations of the c-kit or PDGFRA exist in most of GIST, and a few patients have different exons of double mutations in c-kit gene or coexistence of double mutations in genes of c-kit and PDGFRA. Classification of gene mutations may guide tumor targe- ting therapy with Imatinib.
出处
《解放军医药杂志》
CAS
2014年第2期34-39,43,共7页
Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
