结直肠癌淋巴结转移与APC、p53和K-ras基因变异的相关性研究
投稿时间:2011-05-03    点此下载全文
引用本文:徐新民,邓周录,钱建畅,王鹏,蔡哲,蔡剑平.结直肠癌淋巴结转移与APC、p53和K-ras基因变异的相关性研究[J].医学研究杂志,2011,40(12):31-36
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作者单位
徐新民 北京协和医学院研究生院、卫生部北京医院/卫生部北京老年医学研究所/卫生部老年医学重点实验室 
邓周录 中日友好医院 
钱建畅 温州医学院药学院药理教研室、卫生部北京医院/卫生部北京老年医学研究所/卫生部老年医学重点实验室 
王鹏 中日友好医院 
蔡哲 中日友好医院 
蔡剑平 卫生部北京医院/卫生部北京老年医学研究所/卫生部老年医学重点实验室 
中文摘要:目的探讨结直肠癌淋巴结转移与APC、p53和K-ras基因变异的相关性。方法用组织DNA抽提试剂盒提取32例淋巴结转移和20例无淋巴结转移的结直肠癌组织DNA,用DHPLC法对APC基因第15号外显子突变富集区(mutation cluster region,MCR)和p53基因的第4~9外显子进行基因变异初筛,对K-ras第12、13和61密码子采用PCR产物直接测序进行基因变异初筛,并用基因克隆测序法进行各变异位点确认。结果APC基因在淋巴结转移患者癌组织中的突变频率显著高于无淋巴结转移患者(53.1% vs 15.0% P=0.006),在Ⅲ和Ⅳ期患者癌组织中突变频率显著高于Ⅰ和Ⅱ期患者(60.0% vs 10.5%,P=0001),在肝转移患者癌组织中的突变频率显著高于无肝转移患者(85.7% vs 31.1%,P=0.006)。结论本研究结果显示APC基因MCR的基因变异可能是结直肠癌淋巴结转移的重要生物标志,也可能是临床分级及肝转移的重要生物标志。
中文关键词:结直肠癌  淋巴结转移  APC基因
 
Correlation between APC, p53, K-ras and Colorectal Cancer with Lymph Node Metastasis
Abstract:ObjectiveTo study the relationship between alterations in APC, p53, K-ras and colorectal cancer with lymph node metastasis. MethodsWe used tissue DNA extraction kit to extract DNA in 32 cases lymph node metastasis tissues and 20 cases free of lymph node metastasis tissues. Exon 4~9 of p53 gene and mutation cluster region (MCR) of APC gene were analyzed by DHPLC as a screening method and PCR product sequencing were performed to detect the mutation in codon 12, 13 and 61 for K-ras gene. All the variations were confirmed by clone sequencing. ResultsMutation frequency in APC gene was significantly associated with lymph node metastasis (53.1% vs 15.0%,P=0.006), high-stage tissues (60.0% vs 10.5%,P=0.001), liver metastasis (85.7% vs 31.1%,P=0.006) respectively. ConclusionOur results showed that MCR region in APC may be an important biomarker of colorectal cancer with lymph node metastasis and may also indicate high degree of malignancy and lymph node metastasis.
keywords:Colorectal cancer  Lymph node metastasis  APC gene
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