Identification and extensive analysis of inverted-duplicated HBV integration in a human hepatocellular carcinoma cell line.
Hepatitis B virus (HBV) DNA is often integrated into hepatocellular carcinoma (HCC). Although the relationship between HBV integration and HCC development has been widely studied, the role of HBV integration in HCC development is still not completely understood. In the present study, we constructed a pooled BAC library of 9 established cell lines derived from HCC patients with HBV infections. By amplifying viral genes and superpooling of BAC clones, we identified 2 clones harboring integrated HBV DNA. Screening of host-virus junctions by repeated sequencing revealed an HBV DNA integration site on chromosome 11q13 in the SNU-886 cell line. The structure and rearrangement of integrated HBV DNA were extensively analyzed. An inverted duplicated structure, with fusion of at least 2 HBV DNA molecules in opposite orientations, was identified in the region. The gene expression of cancer-related genes increased near the viral integration site in HCC cell line SNU-886.
Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do 363-951, Korea.
Jeong
J
Bok
Kwang Joong
KJ
Kim
Mi-Hyun
MH
Park
Seung-Hak
SH
Cho
Hye-Ja
HJ
Lee
Eun-Ju
EJ
Lee
Chan
C
Park
Jong-Young
JY
Lee
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology; D045744:Cell Line, Tumor; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11; D004279:DNA, Viral / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology; D017422:Sequence Analysis, DNA; D016662:Virus Integration
D004279:DNA, Viral