Correlation between DNA methylation and pathological changes in human hepatocellular carcinoma.

BACKGROUND/AIMS: This study was undertaken to obtain information at the molecular level on the possible mechanism of human hepatocarcinogenesis and also to provide a clue for further study.

METHODOLOGY

We examined the methylation patterns of c-myc and c-N-ras oncogenes, which are most closely related to HCC, by using the Southern blot technique and HpaII/MspI restriction enzymes. In addition, we measured the level of global DNA methylation in cancerous and paracancerous tissues of HCC by incubating DNA with 3H-S-adenosylmethionine (3H-SAM) in the presence of methylase. The measured global level of DNA methylation was compared with pathological changes of the liver. The methylation patterns of oncogenes as well as the levels of global DNA methylation were compared with pathological changes.

RESULTS

The results showed that the hypomethylation rates of c-myc and c-N-ras oncogenes were 30% and 61% respectively in human hepatocellular carcinoma, coinciding with a decreased level of global DNA methylation. DNA hypomethylation was highly significant in cases with a tendency of tumor infiltration or metastasis.

CONCLUSIONS

It is concluded that abnormal DNA methylation plays an important role in the process of hepatocellular carcinogenesis. DNA methylation level is closely correlated with the biological characteristic of liver cancer, the lower the level of DNA methylation, the stronger the infiltration and metastatic capacity.