[Characteristics of high frequency 249 codon mutation of p53 gene in hepatocellular carcinoma in prevalent area of China].

OBJECTIVE

To study the characteristic features of an unique hotspot missense mutation of the 249 codon of p53 gene demonstrated in human hepato-cellular carcinoma(HCC) in a region of high(Qidong) and low (Beijing) exposure to both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in China.

METHODS

Surgical samples from 97 HCC from Qidong and 22 from Beijing, China, collected in 1994 through 1997, were studied. The 249 codon mutation of p53 gene was detected by PCR followed by HaeIII RFLP analysis and DNA sequencing. Intracellular p53 protein level was determined by immunohistochemical staining.

RESULTS

High mutation rate of 249 codon of p53 gene was consistently found in recent years, with an average of 53.6% (52/97). No such mutation was identified in 22 Beijing HCC collected in the same time period. The genotype of p53 249 codon mutants which showed heterozygous profile was identified to be homozygous in nature following tumor tissue enrichment. Of 21 HCC shown to have 249 codon mutation, 20 exhibited high intranuclear accumulation of p53 protein. p53 protein staining was negative in the surrounding noncancerous hepatic tissue.

CONCLUSION

The high frequency of homozygous mutation of the 249 codon of p53 gene accompanied with p53 protein accumulation provides important enlightenment in the understanding of hepatocarcinogenesis and clinical application of gene therapy and/or immunotherapy for HCC.