Integration of hepatitis B virus DNA through a mutational hot spot within the cohesive region in a case of hepatocellular carcinoma

Department of Medicine, Queen Elizabeth the Queen Mother Wing, St Mary's Hospital Medical School, South Wharf Street, London W2 1PG, U.K. Integrated hepatitis B virus (HBV) DNA previously cloned from a hepatocellular carcinoma genomic library derived from a Japanese patient was characterized further. Sequence analysis of restriction fragments bearing the virus-host junctions defined 3125 nucleotides of essentially un-rearranged HBV DNA of the adr subtype with the right junction mapping within the cohesive region at position 1970 and the left within the pre-core at position 1886. The right viral-host junction contains a 7 bp repeat (TGTAGGC) and a possible 2 bp inversion. The integrated HBV DNA includes the complete open reading frames for core, pre-S, S and polymerase and a 3' truncated X gene, and lacks most of the pre-core. Integration has occurred at a mutational hot spot of the viral genome and appears to be located in a region of semi-repetitive genomic DNA 3' to the -globin gene cluster. Received 10 June 1991; accepted 10 September 1991.