胃癌4q28位点杂合性缺失的研究与候选基因FAT4表达的验证  

Study on loss of heterozygosity on chromosome 4q28 and expression of gene FAT4 in gastric cancer

作　　者：吴建林[1] 刘卫仁[1] 于颖彦[1] 计骏[1] 张佳年[1] 陈雪华[1] 刘炳亚[1] 朱正纲[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科上海消化外科研究所,上海200025

出　　处：《诊断学理论与实践》2009年第2期155-159,共5页Journal of Diagnostics Concepts & Practice

基　　金：国家科技部"十一五""863"重大专项资助项目(2006AA02A402;2006AA02A301);国家自然科学基金资助项目(30572127;30770961;30670939);上海市浦江人才计划资助项目(PJ200700367);上海市科委重点基础研究资助项目(05JC14013)

摘　　要：目的:研究胃癌组织中4q28位点杂合性缺失(LOH)的频率,并验证该位点候选基因FAT4mRNA表达情况。方法:在4q28位点选择与FAT4连锁的2个微卫星标记D4S2975和D4S1644,应用PCR产物毛细管电泳法分析68例手术切除的胃癌标本中这2个微卫星位点的LOH频率;应用RT-PCR法验证9个胃癌细胞株及39例新鲜胃癌加配对正常组织中该位点FAT4mRNA的表达水平。将相关检测结果与多种临床病理参数进行比较分析。结果:68例胃癌组织中D4S2975和D4S1644位点的LOH频率分别为35.56%(16/45)和40.74%(11/27),2个微卫星位点平均LOH频率为38.15%。检测39例新鲜胃癌及配对正常组织的FAT4mRNA表达水平,其中12例(30.77%)胃癌组织的FAT4mRNA表达较其配对正常组织明显下降。经与多种临床病理参数比较分析发现,FAT4mRNA表达下调与胃底贲门部胃癌密切相关(P=0.029),40岁以下青年型胃癌有FAT4表达丢失倾向,但差异无统计学意义(P=0.095)。结论:胃癌中4q28位点存在较高频率的LOH,对该位点内候选抑癌基因FAT4mRNA表达验证显示,部分胃癌组织存在FAT4表达下调,该基因下调与胃癌的发生部位及患者年龄间可能存在一定关系。Objective To investigate loss of heterozygosity （LOH） on chromosome 4q28 and expression of gene FAT4 in gastric cancer. Methods PCR product capillary electrophoresis was used to analyze the LOH frequency of 2 microsatellite markers D4S2975 and D4S1644 linked to FAT4 gene at 4q28 locus in 68 surgical resected gastric cancer specimens. RT-PCR was used to detect the mRNA expression level of gene FAT4 in 9 gastric cancer cell line and 39 paired normal and gastric cancer tissue specimens. The association between LOH on 4q28, FAT4 mRNA expression level and clinicopathological parameters was analyzed. Results The frequencies of LOH in D4S2975 and D4S1644 were 35.56% （16/45）and 40.74% （11/27）, respectively, with an average of 38.15%. The expression of FAT4 mRNA was reduced in 12 of 39 specimens of gastric cancer. The down-regulation of FAT4 mRNA expression had close correlation with location of tumor at the cardia and the fundus （P=0.029）, and was more often observed in young adult patients under 40 years of age （P=0.095）. Conclusions Higher frequency of LOH on 4q28 is identified in gastric cancer. The mRNA expression of gene FAT4 decrease in some of the gastric cancer. The down-regulation of FAT4 gene may have some correlation with tumor location and age of patient.

关 键 词：胃肿瘤 FAT4基因 基因表达 杂合性缺失 

分 类 号：R735.2[医药卫生—肿瘤]