Mutation of p53 gene in regenerative nodules in cirrhotic liver

Mutations of p53 gene have been detected in precancerous stages of several cancers, and the possible role in multistep carcinogenesis is suggested. The aim of this study was to examine the mutation profile of p53 gene in regenerative nodules in cirrhotic livers.

Ninety eight tissue specimens of regenerative nodules obtained from 15 cases of cirrhosis were used for analysis. Twenty cases of chronic hepatitis and two cases of fatty liver were used as controls. DNA was extracted from each of manually demarcated regenerative nodules, and nucleotide sequence analysis was performed on p53 gene exon 5.

Direct sequencing detected p53 mutations in seven of 98 DNA samples (7.1%) from regenerative nodules in six cases of cirrhosis. Subcloning analysis revealed that mutation sites differed in each subclone and the incidences of the mutation varied from 7.7 to 58.8% depending on individual nodules. The mutation was not detected in any of chronic hepatitis and fatty liver. There were inconsistent p53 sequence with regenerative nodules and accompanied hepatocellular carcinomas in six cases.

Mutations of p53 gene were frequently found in cirrhotic livers compared with livers of patients with chronic hepatitis (P<0.01), suggesting that p53 mutations at the stage of cirrhosis may be a causative factor that may potentially lead to hepatocellular carcinoma.