CAJ | 학술논문

背景:微卫星不稳是一种重要的基因改变方式,在肿瘤的发生中起重要作用,其发生是由于错配修复基因发生缺陷所致.错配修复基因hMLH1突变在遗传性非息肉性大肠癌中的作用已有报道,但在散发性大肠癌的作用尚缺乏深入的研究.目的:探讨错配修复基因hMLH1突变在大肠癌发生中的作用及与微卫星不稳的关系.设计:单一样本实验.单位:解放军第三军医大学西南医院消化科.材料:76例大肠癌及相应正常组织均为2001-01/2003-12西南医院外科手术切除标本,所有患者均无肿瘤家族史,并未接受过放疗和化疗,对实验知情同意.方法:采用二维DNA电泳和DNA测序技术检测hMLH1突变;采用聚合酶链反应为基础的方法检测微卫星不稳.主要观察指标:①大肠癌hMLH1突变及微卫星不稳检出率.②微卫星不稳与hMLH1突变的关系.结果:①76例大肠癌中检出hMLH1基因突变8例,突变率为10.5%,检出微卫星不稳20例,检出率为26.3%.右侧大肠癌hMLH1突变和微卫星不稳的检出率显著高于左侧大肠癌(6/26比2/50,x2=4.739,P=0.029;11/26比9/50,x2=5.212,P=0.022),hMLH1突变和微卫星不稳与肿瘤大小、分化程度、组织学类型、浸润深度、淋巴结转移和临床病理分期无显著相关.②将微卫星不稳分为高频率微卫星不稳(≥2个位点)10例、低频率微卫星不稳(仅为1个位点)10例和微卫星不稳阴性56例3组,8例hMLH1基因突变均发生于高频率微卫星不稳组,而低频率微卫星不稳和微卫星不稳阴性组未见有突变者.结论:hMLH1基因突变与微卫星不稳多发生于右侧大肠癌,hMLH1突变与高频率微卫星不稳大肠癌的发生有关.
배경:미위성불은시일충중요적기인개변방식,재종류적발생중기중요작용,기발생시유우착배수복기인발생결함소치.착배수복기인hMLH1돌변재유전성비식육성대장암중적작용이유보도,단재산발성대장암적작용상결핍심입적연구.목적:탐토착배수복기인hMLH1돌변재대장암발생중적작용급여미위성불은적관계.설계:단일양본실험.단위:해방군제삼군의대학서남의원소화과.재료:76례대장암급상응정상조직균위2001-01/2003-12서남의원외과수술절제표본,소유환자균무종류가족사,병미접수과방료화화료,대실험지정동의.방법:채용이유DNA전영화DNA측서기술검측hMLH1돌변;채용취합매련반응위기출적방법검측미위성불은.주요관찰지표:①대장암hMLH1돌변급미위성불은검출솔.②미위성불은여hMLH1돌변적관계.결과:①76례대장암중검출hMLH1기인돌변8례,돌변솔위10.5%,검출미위성불은20례,검출솔위26.3%.우측대장암hMLH1돌변화미위성불은적검출솔현저고우좌측대장암(6/26비2/50,x2=4.739,P=0.029;11/26비9/50,x2=5.212,P=0.022),hMLH1돌변화미위성불은여종류대소、분화정도、조직학류형、침윤심도、림파결전이화림상병리분기무현저상관.②장미위성불은분위고빈솔미위성불은(≥2개위점)10례、저빈솔미위성불은(부위1개위점)10례화미위성불은음성56례3조,8례hMLH1기인돌변균발생우고빈솔미위성불은조,이저빈솔미위성불은화미위성불은음성조미견유돌변자.결론:hMLH1기인돌변여미위성불은다발생우우측대장암,hMLH1돌변여고빈솔미위성불은대장암적발생유관.
BACKGROUND: Microsatellite instability (MSI), an important gene change type, plays animportant role in the occurrence of tumor. Mismatch repair gene induces its occurrence. Although the effect of mismatch repair gene hMLH1 mutation in the hereditary nonpolyposis colorectal cancers (HNPCC) has been reported, its effect on the sporadic colorectal carcinoma lacks in-depth study.OBJECTIVE: To investigate the effect of mismatch repair gene hMLH1 mutation on colorectal carcinogenesis, and its correlation with MSI.DESIGN: Single-sample experiment.SETTING: Department of Gastroenterology, Southwest Hospital of Third Military Medical University of Chinese PLA.PARTICIPANTS: Seventy-six cases of sporadic colorectal carcinoma and corresponding normal tissues were obtained from surgically resected specimens of coloreetal carcinoma in Southwest Hospital between January 2001and December 2003. No patients had family history of tumor, or had received radiotherapy and chemotherapy. Patients were informed of the experiment.METHODS: Mutation of hMLH1 was detected by two-dimensional electrophoresis and DNA sequencing; MSI was analyzed by PCR-based methods.MAIN OUTCOME MEASURES: ① Detection rate of hMLH1 mutation of colorectal carcinoma and MSI. ② The relationship of MSI and hMLH1 mutation.RESULTS: Seventy-six cases of sporadic colorectal carcinoma were studied for hMLH1 mutation and MSI. hMLH1 mutation was detected in 8 (10.5%) cases of colorectal carcinomas while MSI was detected in 20 (26.3%) cases of colorectal carcinomas. Frequency of hMLH1 mutation and MSI was significantly higher in right colorectal cancer than in left colorec tal cancer (6/26 vs 2/50, x2=4.739, P=0.029; 11/26 vs 9/50,x2=5.212,P=0.022). No association was observed between hMLH1 mutation or MSI and tumor size, differentiation, histological type, depth of invasion, metastasis or clinical pathological stages. ② MSI was divided into high-frequency group (≥ 2 loci, n=10) and low-frequency group (1 locus, n-10), and MSI negative group (n=56). 8 hMLH1 mutations were all detected in high frequency MSI group, but no mutation was found in low frequency MSI or MSI negative groups.CONCLUSION: hMLH1 mutation and MSI occur in cancer of the right large intestine and hMLH1 mutation is involved in carcinogenesis of some sporadic colorectal cancer with high-frequency MSI.