Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 15, 2003; 9(4): 692-695
Published online Apr 15, 2003. doi: 10.3748/wjg.v9.i4.692
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
Xing-Hua Huang, Lu-Hong Sun, Dong-Dong Lu, Yan Sun, Li-Jie Ma, Xi-Ran Zhang, Jian Huang, Long Yu
Xing-Hua Huang, Li-Jie Ma, Long Yu, The State Key Laboratory of Genetic Engineering, Fudan University, 200433, Shanghai, China
Lu-Hong Sun, Dong-Dong Lu, Xi-Ran Zhang, School of life sciences, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China
Xing-Hua Huang, Yan Sun, Jian Huang, Qidong Liver Cancer Institute, Qidong 226200, Jiangsu Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Long Yu, The State Key Laboratory of Genetic Engineering, Fudan University, 200433, Shanghai, China.
Telephone: +86-21-65643954 Fax: +86-21-65643250
Received: August 2, 2002
Revised: August 20, 2002
Accepted: August 27, 2002
Published online: April 15, 2003

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 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 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 249Ser p53 mutation should be developed to a new early diagnostic marker for HCC.

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