Integration of Region X of Hepatitis B Virus Genome in Human Primary Hepatocellular Carcinomas Propagated in Nude Mice

Tissues of human primary hepatocellular carcinoma (PHC) from six patients infected with hepatitis B virus (HBV) were propagated in nude mice, as well as a strain of hepatitis B surface antigen-positive PHC (PLC/PRF/5). Integration of viral DNA into chromosomal DNA of tumour cells was evaluated by the capacity to hybridize with radiolabelled DNA probes, each representing fundamental parts of the HBV genome, that is S and C genes and regions pre-S and X. All PHC cells possessed region X integrated in their chromosomes. However, integration of the S gene, C gene and region pre-S was found in only six of the seven PHCs. Based on these findings, the integration of region X seems to be most closely associated with carcinogenesis in HBV infection. Epidemiological surveys (Szmuness, 1978; Beasley et al., 1981) indicate a close correlation between infection with hepatitis B virus (HBV) and the incidence of primary hepatocellular carcinoma (PHC). Moreover, DNA sequences of HBV (HBV-DNA) are integrated into genomic DNA of most patients with PHC seropositive for hepatitis B surface antigen (HBsAg), and also in an HBsAg-positive hepatoma cell line (Brechot et al., 1980; Edman et al., 1980