CORRELATION BETWEEN DNA METHYLATION AND PATHOLOGICAL-CHANGES IN HUMANHEPATOCELLULAR-CARCINOMA

BACKGROUND/AIMS: This study was undertaken to obtain information at th e molecular level on the possible mechanism of human hepatocarcinogene sis and also to provide a clue for further study. METHODOLOGY: We exam ined the methylation patterns of c-myc and c-N-ras oncogenes, which ar e most closely related to HCC, by using the Southern blot technique an d HpaII/MspI restriction enzymes. In addition, we measured the level o f global DNA methylation in cancerous and paracancerous tissues of HCC by incubating DNA with H-3-S-adenosylmethionine (H-3-SAM) in the pres ence of methylase. The measured global level of DNA methylation was co mpared with pathological. changes of the liver. The methylation patter ns of oncogenes as well as the levels of global DNA methylation were c ompared with pathological changes. RESULTS: The results showed that th e hypomethylation rates of c-myc and c-N-ras oncogenes were 30% and 61 % respectively in human hepatocellular carcinoma, coinciding with a de creased level of global DNA methylation. DNA hypomethylation was highl y significant in cases with a tendency of tumor infiltration or metast asis. CONCLUSIONS: It is concluded that abnormal DNA methylation plays an important role in the process of hepatocellular carcinogenesis. DN A methylation level is closely correlated with the biological characte ristic of liver cancer, the lower the level of DNA methylation, the st ronger the infiltration and metastatic capacity.