nm23-H1基因突变及异常表达与大肠癌转移相关性的研究-东南大学学报医学版

nm23-H1基因突变及异常表达与大肠癌转移相关性的研究

单位：1.东南大学基础医学院病理学教研室,江苏南京,210009； 2.柳州铁路中心医院病理科,广西柳州545007； 3.江苏省肿瘤研究所分子生物学研究室,江苏南京,210009

分类号：R735.34, R73.37, Q386, Q754

出版年·卷·期（页码）：2002·21·第一期（44-48）

摘要：

目的:探讨nm23-H1基因突变及异常表达与大肠癌转移之间的关系.方法:(1)收集63例中国人大肠癌组织及癌旁组织,酚-氯仿-异戊醇法提取基因组DNA,同时收集整理患者的临床和病理资料;(2)应用PCR扩增nm23-H1基因全部编码序列第2～5位外显子后,经SSCP法初步筛查基因突变并对异常带型样本进行DNA测序分析;(3)应用流式细胞仪检测14对大肠癌组织及癌旁组织nm23-H1蛋白的表达情况.结果:nm23-H1基因第2～4位外显子在63例大肠癌组织中(其中20例标本有淋巴结转移)未发现异常突变;仅有15例大肠癌组织nm23-H1基因第5外显子序列存在突变,其第360位碱基发生T-C置换(同义突变);nm23-H1基因蛋白在大肠粘膜组织中有表达,在部分大肠癌组织中的表达比其癌旁粘膜组织低,并与肿瘤转移有相关性.结论:nm23-H1基因突变在大肠癌组织中为小概率事件,大肠癌病理类型、有无转移与nm23-H1基因突变无明显相关性;nm23-H1基因蛋白水平的表达下降与大肠癌的转移有相关性.

Objective To investigate the role of nm23?H1 mutation in the metastasis of colorectal cancer and the relationship between nm23?H1 gene and the colorectal cancer on differentiation and clinical prognosis.Methods The mutation of nm23?H1 exons 2,3,4 and 5 were detected.DNA were extracted from 63 colorectal cancer tissue using salt out extraction method and DNA sequencer corresponding to the coding region of nm23 were amplified by polymerase chain reaction (PCR). Single stranded conformation polymorphism(SSCP) and direct sequencing were performed.Flow cytometry (FCM) was used to analyze the expression level of nm23?H1 protein in 14 matched colorectal tissue samples.Results No mutation in the exons 2,3,4 of Nm23?H1 in 63 colorectal cancer samples was detected.15 of 63 samples exhibited an abnormal shift SSCP band in exon 5 of nm23?H1 gene and subsequent DNA sequencing showed T→C transition at position 360 that led to same?sense mutation.There were no relationship between nm23?H1 mutation and the metastasis of colorectal cancer. nm23?H1 protein expression level was lower in colon tumors than that in matched normal mucosa,moreover,the protein expression levels in 3 cases of metastasis were significantly different from those in colorectal cancers.Conclusion nm23?H1 mutations may be a rare event in colon tumors.nm23?H1 gene mutation do not play an important role in the metastasis of colon tumors;the expression of nm23?H1 protein is inversely associated with high metastatic potential of colon tumors.

参考文献：

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