Codon 249 mutation in exon 7 of p53 gene in plasma DNA:maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area,China  

作　　者：Xing-HuaHuang Lu-HongSun Dong-DongLu YanSun Li-JieMa Xi-RanZhang JianHuang LongYu 

机构地区：[1]TheStateKeyLaboratoryofGeneticEngineering,FudanUniversity,200433,Shanghai,China [2]Schooloflifesciences,NanjingNormalUniversity,Nanjing210097,JiangsuProvince,China [3]QidongLiverCancerInstitute,Qidong226200,JiangsuProvince,China

出　　处：《World Journal of Gastroenterology》2003年第4期692-695,共4页世界胃肠病学杂志（英文版）

摘　　要：AIM: One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene (1,20),and it has been identified as a 'hotspot' mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2, 3, 9, 10, 16, 24). We evaluated in this paper whether this 'hotspot' mutation could be detected in cellfree DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker.METHODS: We collected blood samples from 25hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 μl of plasma from each sample. The 249ser p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products.RESULTS: We found in exon 7 of p53 gene G→T transversion at the third base of codon 249 resulting 249Arg→249ser mutation in 10/25 (40%) hepatocellular carcinoma cases,4/20 (20%) cirrhotics, and 2/30 (7 %) healthy controls.The adjusted odds ratio for having the mutation was 22.1(95 % CI, 3.2～91.7) for HCC cases compared to controls.CONCLUSION: These data show that the 249ser p53mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation was also detected, although it was at a much lower frequency,in plasma DNA of Qidong cirrhotics and healthy controls;We consider that these findings, together with the usual method of HCC diagnosis, will give more information in early diagnosis of HCC, and 249ser p53 mutation should be developed to a new early diagnostic marker for HCC.AIM:One of the characteristics of hepatocellular carcinoma (HCC)in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene(1,20), and it has been identified as a'hotspot'mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers(2,3,9,10,16,24).We evaluated in this paper whether this'hotspot'mutation could be detected in cell- free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong,China,and tried to illustrate the significance of the detection of this molecular biomarker. METHODS:We collected blood samples from 25 hepatocellular carcinoma patients,20 cirrhotic patients and 30 healthy controls in Qidong area.DNA was extracted and purified from 200 μl of plasma from each sample.The 249^(Ser) p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products. RESULTS:We found in exon 7 of p53 gene G→T transversion at the third base of codon 249 resulting 249^(Arg)→249^(Ser) mutation in 10/25(40 %)hepatocellular carcinoma cases, 4/20(20 %)cirrhotics,and 2/30(7 %)healthy controls. The adjusted odds ratio for having the mutation was 22.1 (95%CI,3.2～91.7)for HCC cases compared to controls. CONCLUSION:These data show that the 249^(Ser)p53 mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients.We found this mutation was also detected,although it was at a much lower frequency, in plasma DNA of Qidong cirrhotics and healthy controls; We consider that these findings,together with the usual method of HCC diagnosis,will give more information in early diagnosis of HCC,and 249^(Ser)p53 mutation should be developed to a new early diagnostic marker for HCC.

关 键 词：P53基因 血浆 DNA 肝细胞癌 肿瘤标志物 早期诊断 高发地区 

分 类 号：R735.7[医药卫生—肿瘤]