Inactivation of tumor suppressor gene is believed to be important in the development of many hyman malignancies. Recently, several lines of evidence have indicated that the wild-type p53 gene, located at chromosome 17p13.1, may function as a
tumor
suppressor gene and that a mutant p53 gene could promote transformation by inactivating noramal p53 function in a dominant negative fashion. In addition to gross DNA abnormalities, many different point mutations in highly conserved regions of the
open
reading frame have been observed in a variety of common cancers, such as lung, colon, and breast cancers.
In hepatocellular carcinoma(HCC) from Quidong in China and southern Africa, known mutations of the p53 gene include selective guaine to thymine(G to T) transversions, which tend to cluster at codon 24.9. This mutational specificity could reflect
exposure to specific carcinogen such as aflatoxin B1. In the current study, Southern blot analysis, PCR-SSCP, and nucleotide sequencing were performed to evaluate the loss of heterozygosity(LOH) on chromosome 17p and structural abnormalities of
p53
gene
in the hepatoma tissues from Korean patients and in established HCC cell lines.
A cell line sample of Hep-3B showed partial deletion of p53 gene but contained no mutation in the open reading frame. Three HCC tissue samples out of seven informative cases demon strated LOH at chromosome 17p but no p53 gene mutation in those
samples.
In this study, only one out of thirteen HCC tissue samples from Korean patients revelaled p53 gene mutation at codon 244, which was G to A transition(from GGC to GAC). P53 gene mutation is relatively rare in hepatoma from Korean patients
especially
at
codon 249.
The mutational pattern and frequency of p53 gene in the hepatoma suggested that hepatitis B viral infection appears to be more important than aflatoxin B1 in hepato-carcinogenesis in Korea.
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