大肠肿瘤APC基因突变的研究  

Mutation of APC gene in sporadic colorectal tumors

作　　者：余成仿[1,2] 王吉甫[1,2] 

机构地区：[1]暨南大学医学院附属医院外科 [2]中山医科大学附属第一医院胃肠外科

出　　处：《中华肿瘤杂志》1998年第5期348-350,共3页Chinese Journal of Oncology

摘　　要：目的检测ＡＰＣ基因在国人散发性大肠肿瘤中的突变情况，并探讨ＡＰＣ基因突变与大肠肿瘤生物学行为的关系。方法采用ＰＣＲＳＳＣＰ、ＤＮＡ测序对２７例（３３份标本）大肠息肉，３６例大肠癌和相应正常粘膜及３例家族性腺瘤性息肉瘤（ＦＡＰ）标本中ＡＰＣ基因“突变密集区”（ｍｕｔａｔｉｏｎｃｌｕｓｔｅｒｒｅｇｉｏｎＭＣＲ）的突变进行了研究。结果大肠息肉和癌组织中，ＡＰＣ基因ＭＣＲ突变率分别为３０．３％（１０／３３）和３５．９％（１４／３９），两者差异无显著性，而正常大肠粘膜、炎性息肉和增生性息肉均无突变。３例ＦＡＰ发现有２例突变，其中１例从正常粘膜到腺瘤、到癌变组织均有突变，另１例则在＞１．０ｃｍ的腺瘤和肝转移癌组织有突变，测序结果证实该例在１４２５号密码子存在相同点突变。ＡＰＣ突变与肿瘤的临床病理特征无明显的相关性。结论ＡＰＣ不仅在ＦＡＰ中存在突变，而且在散发性大肠肿瘤中亦存在突变；它的突变至少参与了部分大肠癌的发生发展过程，而且是这一过程中较早发生的事件。Objective To investigate mutation of APC gene in sporadic colorectal tumors. Methods Thirty six samples of colorectal cancer and twenty eight samples of colorectal polyps resected by operation and endoscopy were collected. As control, normal mucosal tissues in patients with cancer were taken from site 10 cm away from cancer. Three familial adenomatous polyposis (FAP) patients were also included in this study. The mutation cluster region (MCR) within exon 15 of APC gene was amplified by PCR and the PCR products were subject to SSCP analysis. Three mutant DNA fragments screened by PCR SSCP were sequenced. Results No mutation in MCR of APC gene was found in normal mucosa ,inflammatory polyp and hyperplastic polyp. Mutation in MCR of APC gene was found in 7 of 28 cases with sporadic colorectal polyps and in 11 of 36 cases with colorectal carcinomas. The difference in mutation frequency between adenomatous group (including FAP,31.0%) and carcinomatous group(including FAP,35.9%) was not statistically significant ( P >0.05).Mutation of APC gene was detected in two of three FAP patients. The same point mutation of codon 1 425 was found in both adenoma tissue and its hepatic metastasis in one FAP patient by DNA sequencing. Conclusion Mutation of APC gene occurs not only in FAP, but also in sporadic colorectal tumors.It takes part in the development of most, if not all,sporadic colorectal carcinomas.

关 键 词：大肠肿瘤 APC基因 基因突变 病理学 

分 类 号：R735.34[医药卫生—肿瘤]