家族性腺瘤性息肉病患者APC基因启动子区异常甲基化及大片段结构异常  

Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis

作　　者：张元颖[1] 陈森清[1] 朱明[1] 李金田[1] 马国建[1] 张晓梅[1] 周建农[2] 

机构地区：[1]江苏省肿瘤防治研究所遗传与分子生物室,南京210009 [2]江苏省肿瘤医院结直肠外科

出　　处：《中华医学遗传学杂志》2008年第4期378-381,共4页Chinese Journal of Medical Genetics

基　　金：江苏省卫生厅重点医学项目（H2009;H200503）：江苏省肿瘤防治研究所青年科技基金（ZQ200409;ZQ200403）

摘　　要：目的研究3个家族性腺瘤性息肉病（familial adenomatous polyposis，FAP）家系的腺瘤样息肉病（adenomatus polyposis coli）基因（ARC）启动子1A区异常甲基化及DNA大片段结构异常。方法对3个FAP家系成员的肿瘤组织标本和正常组织标本DNA进行化学修饰，应用甲基化特异PCR（methylation—specif-ic PCR，MSP）和DNA序列分析方法筛查APC基因启动子1A区甲基化情况。采用多重连接依赖性探针扩增（multiplex ligation—dependent probeam plification，MIJPA）分析系统检测5例FAP患者肿瘤组织标本和正常标本的APC基因的15个外显子及启动子区DNA大片段结构异常。结果在1个家系中发现2例患者存在APC基因启动子1A区异常甲基化。同一个家系中另1例患者存在APC基因全基因杂合性缺失。结论APC基因启动子1A区异常甲基化可影响APC功能，可能是结直肠癌进展过程中的早期事件；大片段缺失可能是导致典型FAP的一个因素。Objective To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli （APC） gene in 3 familial adenomatous polyposis （FAP） pedigrees and to screen large fragment deletions in the APC gene. Methods DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR （MSP） and DNA sequencing. Multiplex ligation-dependent probe amplification （MLPA） was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene. Results No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family. Conclusion Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.

关 键 词：家族性腺瘤性息肉病 腺瘤样息肉病基因 甲基化 甲基化特异聚合酶链反应 杂合性丢失 

分 类 号：R686[医药卫生—骨科学]