Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1984 Sep;3(9):2185–2189. doi: 10.1002/j.1460-2075.1984.tb02111.x

Amplification and rearrangement in hepatoma cell DNA associated with integrated hepatitis B virus DNA.

S Koch, A F von Loringhoven, P H Hofschneider, R Koshy
PMCID: PMC557663  PMID: 6092065

Abstract

DNA of hepatitis B virus is found to be integrated into the genome of infected human liver cells and may be related to the development of primary liver carcinoma. We have previously reported the cloning of cellular DNA with integrated HBV sequences from the PLC/PRF/5 cell line which derives from a human primary liver carcinoma. Two clones, designated as A-10.7 and A-10.5, and a third uncloned fragment are compared by restriction enzyme mapping, hybridization and nucleotide sequencing. The results indicate that amplification of integrated viral DNA and host flanking regions has occurred, followed by transposition and/or major deletions. The implications of these findings for the development of primary liver carcinoma are discussed.

Full text

PDF
2189

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J. J., Bey E. M., Geddes E. W., Lecatsas G. Establishment of a continuously growing cell line from primary carcinoma of the liver. S Afr Med J. 1976 Dec 18;50(54):2124–2128. [PubMed] [Google Scholar]
  2. Beasley R. P., Hwang L. Y., Lin C. C., Chien C. S. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981 Nov 21;2(8256):1129–1133. doi: 10.1016/s0140-6736(81)90585-7. [DOI] [PubMed] [Google Scholar]
  3. Benedict W. F., Murphree A. L., Banerjee A., Spina C. A., Sparkes M. C., Sparkes R. S. Patient with 13 chromosome deletion: evidence that the retinoblastoma gene is a recessive cancer gene. Science. 1983 Feb 25;219(4587):973–975. doi: 10.1126/science.6336308. [DOI] [PubMed] [Google Scholar]
  4. Brechot C., Pourcel C., Louise A., Rain B., Tiollais P. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature. 1980 Jul 31;286(5772):533–535. doi: 10.1038/286533a0. [DOI] [PubMed] [Google Scholar]
  5. Bréchot C., Hadchouel M., Scotto J., Fonck M., Potet F., Vyas G. N., Tiollais P. State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3906–3910. doi: 10.1073/pnas.78.6.3906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chakraborty P. R., Ruiz-Opazo N., Shouval D., Shafritz D. A. Identification of integrated hepatitis B virus DNA and expression of viral RNA in an HBsAg-producing human hepatocellular carcinoma cell line. Nature. 1980 Jul 31;286(5772):531–533. doi: 10.1038/286531a0. [DOI] [PubMed] [Google Scholar]
  7. Clayton C. E., Rigby P. W. Cloning and characterization of the integrated viral DNA from three lines of SV40-transformed mouse cells. Cell. 1981 Aug;25(2):547–559. doi: 10.1016/0092-8674(81)90073-8. [DOI] [PubMed] [Google Scholar]
  8. Cummings I. W., Browne J. K., Salser W. A., Tyler G. V., Snyder R. L., Smolec J. M., Summers J. Isolation, characterization, and comparison of recombinant DNAs derived from genomes of human hepatitis B virus and woodchuck hepatitis virus. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1842–1846. doi: 10.1073/pnas.77.4.1842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dayhoff M. O., Schwartz R. M., Chen H. R., Barker W. C., Hunt L. T., Orcutt B. C. Nucleic acid sequence database. DNA. 1981;1(1):51–58. doi: 10.1089/dna.1.1981.1.51. [DOI] [PubMed] [Google Scholar]
  10. Edman J. C., Gray P., Valenzuela P., Rall L. B., Rutter W. J. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature. 1980 Jul 31;286(5772):535–538. doi: 10.1038/286535a0. [DOI] [PubMed] [Google Scholar]
  11. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  12. Garoff H., Ansorge W. Improvements of DNA sequencing gels. Anal Biochem. 1981 Aug;115(2):450–457. doi: 10.1016/0003-2697(81)90031-2. [DOI] [PubMed] [Google Scholar]
  13. Hiscott J. B., Murphy D., Defendi V. Instability of integrated viral DNA in mouse cells transformed by simian virus 40. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1736–1740. doi: 10.1073/pnas.78.3.1736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klein G. The role of gene dosage and genetic transpositions in carcinogenesis. Nature. 1981 Nov 26;294(5839):313–318. doi: 10.1038/294313a0. [DOI] [PubMed] [Google Scholar]
  15. Koshy R., Koch S., von Loringhoven A. F., Kahmann R., Murray K., Hofschneider P. H. Integration of hepatitis B virus DNA: evidence for integration in the single-stranded gap. Cell. 1983 Aug;34(1):215–223. doi: 10.1016/0092-8674(83)90152-6. [DOI] [PubMed] [Google Scholar]
  16. Koshy R., Maupas P., Müller R., Hofschneider P. H. Detection of hepatitis B virus-specific DNA in the genomes of human hepatocellular carcinoma and liver cirrhosis tissues. J Gen Virol. 1981 Nov;57(Pt 1):95–102. doi: 10.1099/0022-1317-57-1-95. [DOI] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Mougneau E., Birg F., Rassoulzadegan M., Cuzin F. Integration sites and sequence arrangement of SV40 DNA in a homogeneous series of transformed rat fibroblast lines. Cell. 1980 Dec;22(3):917–927. doi: 10.1016/0092-8674(80)90569-3. [DOI] [PubMed] [Google Scholar]
  19. Pasek M., Goto T., Gilbert W., Zink B., Schaller H., MacKay P., Leadbetter G., Murray K. Hepatitis B virus genes and their expression in E. coli. Nature. 1979 Dec 6;282(5739):575–579. doi: 10.1038/282575a0. [DOI] [PubMed] [Google Scholar]
  20. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  21. Rogers K. B. Concentrating Malaria Parasites in Thin Films. Br Med J. 1946 Jan 5;1(4435):11–12. [PMC free article] [PubMed] [Google Scholar]
  22. Sandberg A. A. A chromosomal hypothesis of oncogenesis. Cancer Genet Cytogenet. 1983 Apr;8(4):277–285. doi: 10.1016/0165-4608(83)90070-5. [DOI] [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES