Possible Down Regulation of the p16 Gene Promoter in Individuals with Hepatocellular Carcinoma

BACKGROUND: The p16 tumor suppressor gene is an important negative regulator of the cell cycle. Inactivation of p16, especially via promoter hypermethylation, has been found in numerous human cancers such as breast, lung, colorectal, and liver. OBJECTIVES: To determine the role of epigenetic methylation in p16 regulation in Iranian patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The methylation pattern in the p16 gene promoter was analyzed by bisulfite direct sequencing in 43 paraffin-embedded formalin-fixed tissues from patients with HCC. In addition, normal specimens from liver graft donors were used as the control group. RESULTS: The bisulfite direct sequencing showed heterozygous hypermethylation in 13.9% of individuals with HCC. Homozygous methylation within the GC-box IV was detected in another 58.1% of the patients. CONCLUSIONS: It is proposed that methylation, but not necessarily hypermethylation, may play a role in the down-regulation of the p16 gene promoter at least in some Iranian patients with HCC.