Specific hepatitis B virus integration in hepatocellular carcinoma DNA through a viral 11-base-pair direct repeat.

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Abstract
Integrated hepatitis B virus (HBV) DNA sequences were cloned from cellular DNA of 2 human liver tumors. The structure of the clones was determined by restriction mapping, and the host-viral DNA junctions were sequenced. In each clone one junction mapped to within an 11-base-pair sequence, 5'' T-T-C-A-C-C-T-C-T-G-C, which is directly repeated near the extremities of the cohesive-end region of the free viral genome. The 2 copies of this sequence are termed DR1 and DR2. While 1 clone carried a host-viral junction within DR1, the second one carried a host-viral junction within DR2. The first 1 or 2 base pairs of the repeat were deleted upon recombination with the host genome, leaving at the junctions a common 9-base-pair segment of HBV DNA, 5'' C-A-C-C-T-C-T-G-C. The other 2 host-viral junctions mapped to the pre-S regoin and to the core region of the viral genome, showing no peculiar feature. Evidently, HBV DNA can integrate via a specific viral DNA sequence.