1887

Abstract

Moloney murine leukaemia virus (MoMLV) markedly accelerates thymic lymphoma development in mice carrying a transgene in which the human c- gene is linked to the CD2 locus control region. To investigate the mechanism of synergy and identify the genes which collaborate with in these clonal tumours, we analysed the sites of MoMLV insertion. Analysis of known viral integration loci revealed only a small number of insertions at -1, -1 and -1. Further cloning and hybridization analysis revealed a new common integration locus, designated -1, which was occupied in 25 out of 77 lymphomas examined, with evidence of multiple clonal insertions in some cases. Mapping relative to established chromosomal markers in interspecific backcross mice located -1 to mouse chromosome 17, distal to -1 and -1. These results suggest that the -1 locus may harbour a novel -collaborating gene which acts as a target for activation in T cell lymphomas.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-3-443
1996-03-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/3/JV0770030443.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-3-443&mimeType=html&fmt=ahah

References

  1. Ben-David Y., Prideaux V. R., Chow V., Benchimol S., Bernstein A. 1988; Inactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemia cell lines induced by Friend murine leukemia virus. Oncogene 3:179–185
    [Google Scholar]
  2. Berns A. 1994; Tumorigenesis in transgenic mice: identification and characterization of synergizing oncogenes. Journal of Cellular Biochemistry 47:130–135
    [Google Scholar]
  3. Blyth K., Terry A., O’Hara M., Baxter E. W., Campbell M., Stewart M., Donehower L., Onions D. E., Neil J. C., Cameron E. R. 1995; Synergy between a human c-myc transgene and p53 null genotype in murine thymic lymphomas: contrasting effects of homozygous and heterozygous p53 loss. Oncogene 10:1717–1723
    [Google Scholar]
  4. Breen M., Deakin L., Macdonald B., Miller S., Sibson R., Tarttelin E., Avner P., Bourgade F., Guenet J. L., Montagutelli X., Poirier C., Simon D., Tailor D., Bishop M., Kelly M., Rysavy F., Rastan S., Norris D., Shepherd D., Abbott C., Pilz A., Hodge S., Jackson I., Boyd Y., Blair H., Maslen G., Todd J. A., Reed P. W., Stoye J., Ashworth A., McCarthy L., Cox R., Schalkwyk L., Lehrach H., Klose J., Gangadharan U., Brown S. 1994; Towards high resolution maps of the mouse and human genomes – a facility for ordering markers to 0.1 cM resolution. Human Molecular Genetics 3:621–627
    [Google Scholar]
  5. Breuer M. L., Cuypers H. T., Berns A. 1989; Evidence for the involvement of pim- 2, a new common proviral insertion site, in progression of lymphomas. EMBO Journal 8:743–748
    [Google Scholar]
  6. Cuypers H. T., Selten G., Quint W., Zijlstra M., Maandag E. R., Boelens W., Van Wezenbeek P., Melief C., Berns A. 1984; Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell 37:141–150
    [Google Scholar]
  7. Cuypers H. T., Selten G., Zjilstra M., De Goede R., Melief C., Berns A. 1986; Tumor progression in murine leukemia virus-induced T-cell lymphomas: monitoring clonal selections with viral and cellular probes. Journal of Virology 60:230–241
    [Google Scholar]
  8. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. 1992; Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119–128
    [Google Scholar]
  9. Haupt Y., Bath M. L., Harris A. W., Adams J. M. 1993; bmi- 1 transgene induces lymphomas and collaborates with myc in tumorigenesis. Oncogene 8:3161–3164
    [Google Scholar]
  10. Hilkens J., Cuypers H. T., Selten G., Berns A. 1986; Genetic mapping of pim- l putative oncogene to mouse chromosome 17. Somatic Cell Molecular Genetics 12:81–88
    [Google Scholar]
  11. Kung H. J., Boerkel C., Carter T. H. 1991; Retroviral mutagenesis of cellular oncogenes: a review with insights into the mechanisms of insertional activation. Current Topics in Microbiology and Immunology 171:1–25
    [Google Scholar]
  12. Levy L. S., Lobelle-Rich P. A., Overbaugh J. 1993; Flvi- 2, a target of retroviral insertional mutagenesis in feline thymic lymphosarcomas, encodes bmi- 1. Oncogene 8:1833–1838
    [Google Scholar]
  13. Lu S. J., Rowan S., Bani M. R., Ben-David Y. 1994; Retroviral integration within the Fli- 2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression. Proceedings of the National Academy of Sciences, USA 91:8398–8402
    [Google Scholar]
  14. Poirier Y., Kozak C., Jolicoeur P. 1988; Identification of a common helper provirus integration site in Abelson murine leukemia virus-induced lymphoma DNA. Journal of Virology 62:3985–3992
    [Google Scholar]
  15. Stewart M. A., Cameron E., Toth S., Campbell M., Mcfarlane R., Onions D., Neil J. C. 1993; Conditional expression and oncogenicity of a human c-myc transgene linked to a human CD2 dominant control region. International Journal of Cancer 53:1023–1030
    [Google Scholar]
  16. Tsatsanis C., Fulton R., Nishigaki K., Tsujimoto H., Levy L. S., Spandidos D., Onions D., Neil J. C. 1994; Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement. Journal of Virology 68:8294–8303
    [Google Scholar]
  17. van der Putten H., Quint W., Van Raau J., Maandag E. R., Verma I. M., Berns A. 1981; M-MuLV-induced leukemo-genesis: integration and structure of recombinant proviruses in tumors. Cell 24:729–739
    [Google Scholar]
  18. Van Lohuizen M., Verbeek S., Krimpenfort P., Domen J., Saris C., Radaszkiewicz T., Berns A. 1989; Predisposition to lymphomagenesis in pim- 1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell 56:673–682
    [Google Scholar]
  19. Van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., Van Der Gulden H., Berns A. 1991; Identification of cooperating oncogenes in Eµ-myc transgenic mice by provirus tagging. Cell 65:737–752
    [Google Scholar]
  20. Verbeek S., Van Lohuizen M., Van Der Valk M., Domen J., Kraal G., Berns A. 1991; Mice bearing the Eµ–myc and Eμ-pim-l transgenes develop pre-B cell leukemia prenatally. Molecular and Cell Biology 11:1176–1179
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-3-443
Loading
/content/journal/jgv/10.1099/0022-1317-77-3-443
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error