Quantitative evaluation of genomic instability as a possible predictor fordevelopment of hepatocellular carcinoma: Comparison of loss of heterozygosity and replication error

Both loss of heterozygosity (LOH) and replication error (RER) are considere d to be phenotypes of genomic instability To unveil the role of the genomic instability in hepatocarcinogenesis, frequencies of LOH and RER were simul taneously determined in 15 hepatocellular carcinomas (HCCs), surrounding no ntumorous liver tissues (SL), and 13 liver tissues with chronic viral hepat itis void of cancer (NC) by referencing peripheral blood leukocytes (PBLs) from the corresponding donor using 18 microsatellite markers spread through out the genome. LOH was significantly frequent in HCC compared with that in SL or NC (P = .005, P = .0003, respectively) and observed preferentially a t particular microsatellite loci, D1S204, D2S123, D8S1106, D9S266, D16S748, and D19S601. Although the higher prevalence of RER was also significant in HCC compared with that in NC (P = .03), in most cases the errors were dete cted at very low frequencies and random loci. Both LOH and RER tended to ap pear more prevalently in SL than in NC. The occurrence rate of LOH was high er in the tissues associated with hepatitis B virus (HBV) than with hepatit is C virus (HCV) infection especially in HCC (P = .03). When referencing SL instead of PBLs, the prevalence of LOH and RER in HCC significantly decrea sed (P = .02 and P = .03, respectively). These results suggest that: LOH is closely associated with multistep hepatocarcinogenesis especially under HB V infection, but RER is imperceptibly associated. The quantitative evaluati on of the frequency of LOH by referencing PBLs may be a useful predictor fo r HCC development in chronic liver diseases.