肝细胞癌组织中p53基因突变的研究

目的探讨黄曲霉素（ＡＦＢ１）污染严重的南宁地区的肝细胞癌（ＨＣＣ）与ｐ５３基因突变的关系。方法采用聚合酶链反应限制性片段长度多态性分析,检测６５例ＨＣＣ患者的ｐ５３基因第７外显子点突变。结果３８例ＨＣＣ的ｐ５３基因第２４９密码子有集中的点突变,突变频率为５８５％;伴有乙型肝炎病毒阳性者ｐ５３基因突变率５７４％,阴性者６３６％;高度分化、中度分化和低度分化ＨＣＣ的ｐ５３基因突变率分别为１００％、５５２％和８０８％;伴ＨＣＣ转移者ＨＣＣ的ｐ５３基因突变率为８８９％,未转移者为４６８％。结论ＡＦＢ１是产生ｐ５３基因突变热点的主要原因,而乙型肝炎病毒则具有协同作用;ｐ５３基因突变与ＨＣＣ的分化程度及转移有关,并预示着ＨＣＣ的恶性程度,可能是一个具有重要意义的预后指标

p53 gene mutation in hepatocellular carcinoma

OBJECTIVE: To study the relationship between mutation of p53 gene and hepatocellular carcinoma (HCC). METHOD: Sixty-five cases of HCC from Nanning prefecture of high aflatoxin (AFB1) exposure were studied by polymerase chain reaction and restrictive fragment length polymorphism (PCR-RFLP) analysis to examine the exon 7 of p53 gene in HCC. RESULT: 58.5% of the cases were found to show mutation at codon 249 of p53 gene; 63.6% for the HCCs with HBsAg negative, and 57.4% for those with HBsAg positive; 88.9% for those with metastasis, and 46.8% for those with no metastasis. The mutation rate of p53 gene was 10.0%, 55.2% and 80.8% in the well-, moderately- and poorly-differentiated HCC respectively. CONCLUSION: AFB1 is the most important agent for the mutation at the hot-spot, and hepatitis B virus is the synergistic risk factor. Further study indicated that the p53 gene mutation is correlated with the differentiation and the metastasis of HCC and may serve as an important prognostic factor.