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. 1989 Jan;8(1):133–136. doi: 10.1002/j.1460-2075.1989.tb03357.x

N-myc is frequently activated by proviral insertion in MuLV-induced T cell lymphomas.

M van Lohuizen 1, M Breuer 1, A Berns 1
PMCID: PMC400781  PMID: 2653809

Abstract

We report a new common proviral insertion site in murine leukemia virus-induced T cell lymphomas to be N-myc. Proviral activation of N-myc was found in 35% of independently induced primary tumors. The vast majority of the proviral insertions occur within a small segment of the 3'-untranslated region of the N-myc gene, directly downstream of the protein-encoding domain. This results in an increased level of expression of a truncated N-myc mRNA. Together with the previously shown c-myc activation we now find involvement of myc genes in greater than 75% of the primary T cell lymphomas induced by Moloney murine leukemia virus in C57BL10 and BALB/c mice, and show for the first time that N-myc can be over-expressed by a mechanism other than gene amplification.

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Selected References

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  1. Alt F. W., DePinho R., Zimmerman K., Legouy E., Hatton K., Ferrier P., Tesfaye A., Yancopoulos G., Nisen P. The human myc gene family. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):931–941. doi: 10.1101/sqb.1986.051.01.106. [DOI] [PubMed] [Google Scholar]
  2. Chomczynski P., Qasba P. K. Alkaline transfer of DNA to plastic membrane. Biochem Biophys Res Commun. 1984 Jul 18;122(1):340–344. doi: 10.1016/0006-291x(84)90480-7. [DOI] [PubMed] [Google Scholar]
  3. Cuypers H. T., Selten G., Quint W., Zijlstra M., Maandag E. R., Boelens W., van Wezenbeek P., Melief C., Berns A. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984 May;37(1):141–150. doi: 10.1016/0092-8674(84)90309-x. [DOI] [PubMed] [Google Scholar]
  4. DePinho R. A., Hatton K. S., Tesfaye A., Yancopoulos G. D., Alt F. W. The human myc gene family: structure and activity of L-myc and an L-myc pseudogene. Genes Dev. 1987 Dec;1(10):1311–1326. doi: 10.1101/gad.1.10.1311. [DOI] [PubMed] [Google Scholar]
  5. DePinho R. A., Legouy E., Feldman L. B., Kohl N. E., Yancopoulos G. D., Alt F. W. Structure and expression of the murine N-myc gene. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1827–1831. doi: 10.1073/pnas.83.6.1827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Graham M., Adams J. M., Cory S. Murine T lymphomas with retroviral inserts in the chromosomal 15 locus for plasmacytoma variant translocations. 1985 Apr 25-May 1Nature. 314(6013):740–743. doi: 10.1038/314740a0. [DOI] [PubMed] [Google Scholar]
  7. Jaenisch R., Fan H., Croker B. Infection of preimplantation mouse embryos and of newborn mice with leukemia virus: tissue distribution of viral DNA and RNA and leukemogenesis in the adult animal. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4008–4012. doi: 10.1073/pnas.72.10.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kohl N. E., Gee C. E., Alt F. W. Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science. 1984 Dec 14;226(4680):1335–1337. doi: 10.1126/science.6505694. [DOI] [PubMed] [Google Scholar]
  9. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  10. Legouy E., DePinho R., Zimmerman K., Collum R., Yancopoulos G., Mitsock L., Kriz R., Alt F. W. Structure and expression of the murine L-myc gene. EMBO J. 1987 Nov;6(11):3359–3366. doi: 10.1002/j.1460-2075.1987.tb02657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mucenski M. L., Gilbert D. J., Taylor B. A., Jenkins N. A., Copeland N. G. Common sites of viral integration in lymphomas arising in AKXD recombinant inbred mouse strains. Oncogene Res. 1987;2(1):33–48. [PubMed] [Google Scholar]
  12. Nisen P. D., Zimmerman K. A., Cotter S. V., Gilbert F., Alt F. W. Enhanced expression of the N-myc gene in Wilms' tumors. Cancer Res. 1986 Dec;46(12 Pt 1):6217–6222. [PubMed] [Google Scholar]
  13. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  14. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  15. Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Selten G., Cuypers H. T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A. The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases. Cell. 1986 Aug 15;46(4):603–611. doi: 10.1016/0092-8674(86)90886-x. [DOI] [PubMed] [Google Scholar]
  17. Selten G., Cuypers H. T., Zijlstra M., Melief C., Berns A. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 1984 Dec 20;3(13):3215–3222. doi: 10.1002/j.1460-2075.1984.tb02281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Silver J., Buckler C. E. A preferred region for integration of Friend murine leukemia virus in hematopoietic neoplasms is closely linked to the Int-2 oncogene. J Virol. 1986 Dec;60(3):1156–1158. doi: 10.1128/jvi.60.3.1156-1158.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Taya Y., Mizusawa S., Nishimura S. Nucleotide sequence of the coding region of the mouse N-myc gene. EMBO J. 1986 Jun;5(6):1215–1219. doi: 10.1002/j.1460-2075.1986.tb04349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tsichlis P. N., Lohse M. A., Szpirer C., Szpirer J., Levan G. Cellular DNA regions involved in the induction of rat thymic lymphomas (Mlvi-1, Mlvi-2, Mlvi-3, and c-myc) represent independent loci as determined by their chromosomal map location in the rat. J Virol. 1985 Dec;56(3):938–942. doi: 10.1128/jvi.56.3.938-942.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Voronova A. F., Sefton B. M. Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion. Nature. 1986 Feb 20;319(6055):682–685. doi: 10.1038/319682a0. [DOI] [PubMed] [Google Scholar]
  22. Zimmerman K. A., Yancopoulos G. D., Collum R. G., Smith R. K., Kohl N. E., Denis K. A., Nau M. M., Witte O. N., Toran-Allerand D., Gee C. E. Differential expression of myc family genes during murine development. 1986 Feb 27-Mar 5Nature. 319(6056):780–783. doi: 10.1038/319780a0. [DOI] [PubMed] [Google Scholar]

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