Codon 249 mutations of p53 gene in development of hepatocellular carcinoma.
AIM:To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC).METHODS:Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on translation and transcription were studied using SSCP, IHC and RT-PCR/slot hybridization.RESULTS:Codon 249 mutations were detected in 32.9%, LOH detected in 68.4% among the HCC patients.Mutations of condon 249 were accompanied by LOH in 90%.The positive rates of p53 protein and mRNA were 91.3% and 95.7%, in mutational group, both were significantly higher than those in the non-mutational group (91.3% vs 19.1% and 95.7% vs 40.4%, respectively, both P < 0.01). The translation of p53 gene was strongly related to its transcription by correlation analysis( r = 0.8208).CONCLUSION:LOH might play an important role in hepatocarcinogenesis of codon 249 mutation, which could increase both transcription and translation of p53 gene.The increased expression of p53 protein mainly depend on the increased transcription of p53 gene.
Peng
Xiao-Mou
XM
Peng
Wen-Wei
WW
Yao
Ji-Lu
JL