Genetic and epigenetic alterations of tumor related genes in hepatocellular carcinomas

Proc Amer Assoc Cancer Res, Volume 46, 2005 3549 Hepatocellular carcinoma (HCC) is a malignant cancer with poor prognosis. HCC is developed from chronic hepatitis or liver cirrhosis by hepatitis B virus or hepatitis C virus infection, or drinking. It is important to clarify the characteristics of tumors to prevention of tumor progression and develop treatment for HCCs. In the present study, we examined the genetic and epigenetic alterations of tumor related genes in 38 HCCs. Surgically resected HCCs and their adjacent non-tumorous tissues were used for the analysis. Tissues were collected with informed consent. We analyzed genetic alterations in p53, β-catenin, E-cadherin, TGFβ receptor, and ARF/INK4A locus in HCCs. Mutations were analyzed by fluorescence-based PCR-SSCP method using automated DNA sequencer or Genetic Analyser 3100 (ABI). Loss of heterozygosity (LOH) and promoter CpG hypermethylation of tumor suppressor genes were also analyzed. We found mutations and LOH of the p53 gene in 58% and genetic alterations and CpG hypermethylation of ARF/INK4A locus in 42% of HCCs. Mutations of the β-catenin gene was found in 33%, and LOH and CpG hypermethylation of the E-cadherin gene in 58% of HCCs. But, mutation of TGFβRII was observed in 5% of HCCs. In this study, we found most of HCCs had several genetic alterations, however in some HCCs, we did not find genetic and epigenetic alterations of the genes we examined.