Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma

Oncogene volume 18, pages 1745–1753 (1999)Cite this article

Abstract

In Burkitt's lymphoma (BL) cells the proto-oncogene c-myc is juxtaposed to one of the immunoglobulin (Ig) loci on chromosomes 2, 14, or 22. The c-myc gene becomes transcriptionally activated as a consequence of the chromosomal translocation and shows preferential usage of promoter P1 over P2, a phenomenon referred to as promoter shift. In order to define the responsible regulatory elements within the Ig λ locus, we studied the effect of the human Ig λ enhancer (HuEλ) on c-myc expression after stable transfection into BL cells. A 12 kb genomic fragment encompassing HuEλ, but not HuEλ alone, strongly activated c-myc expression and induced the promoter shift. To identify additional elements involved in c-myc deregulation, we mapped DNaseI hypersensitive sites within the 12 kb λ fragment on the construct. Besides one hypersensitive site corresponding to HuEλ, three additional sites were detected. Two of these elements displayed enhancer activity after transient transfection. The third element did not activate c-myc transcription, but was required for full c-myc activation and promoter shift. Deletion analyses of the c-myc promoter identified the immediate promoter region as sufficient for activation by the Ig λ locus, but also revealed that induction of the promoter shift requires additional upstream elements.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Adams CC and Workman JL. . 1993 Cell 72: 305–308.

  • Anisimova E, Saemundsen AK, Roubal J, Vonka V and Klein G. . 1982 J. Gen. Virol. 58: 163–171.

  • Aronow BJ, Ebert CA, Valerius MT, Potter SS, Wiginton DA, Witte DP and Hutton JJ. . 1995 Mol. Cell. Biol. 15: 1123–1135.

  • Asenbauer H and Klobeck HG. . 1996 Eur. J. Immunol. 26: 142–150.

  • Bergman Y, Rice D, Grosschedl R and Baltimore D. . 1984 Proc. Acad. Natl. Sci. USA 7041–7045.

  • Blasquez VC, Xu M, Moses SC and Garrard WT. . 1989 J. Biol. Chem. 264: 211183–211189.

  • Blomberg B, Rudin CM and Storb U. . 1991 J. Immunol. 147: 2354–2358.

  • Bornkamm GW, Polack A and Eick D. . 1988 George Klein (ed), Marcel Dekker Inc., New York pp. 223–273.

  • Breznick EH and Tze L. . 1997 Proc. Natl. Acad. Sci. 94: 4566–4571.

  • Burkitt DP. . 1958 Br. J. Surg. 46: 218–223.

  • Combriato G and Klobeck HG. . 1991 Eur. J. Immunol. 21: 1513–1519.

  • Cory S. . 1986 Adv. Cancer Res. 47: 189–234.

  • Dalla-Favera R, Bregni M, Erikson J, Ratterson D, Gallo RC and Croce CM. . 1982 Proc. Natl. Acad. Sci. USA 79: 7824–7825.

  • de Wet JR, Wood KV, DeLuca M, Helinski DR and Subramani S. . 1987 Mol. Cell Biol. 7: 725–737.

  • DesJardin E and Hay N. . 1993 Mol. Cell. Biol. 13: 5710–5724.

  • Eick D and Bornkamm GW. . 1986 Nucleic Acid Res. 14: 8331–8346.

  • Eick D and Bornkamm GW. . 1989 EMBO J. 8: 1965–1972.

  • Felsenfeld G. . 1992 Nature 355: 219–224.

  • Forrester WC, Genderen CV, Jenuwein T and Grosschedl R. . 1994 Science 265: 1221–1225.

  • Geltinger C, Hörtnagel K and Polack A. . 1996 Gene Expression 6: 113–127.

  • Glozak MA and Blomberg BB. . 1996 Mol. Immunol. 33: 427–438.

  • Gross DS and Garrard WT. . 1988 Ann. Rev. Biochem. 57: 159–187.

  • Grosveld F, van Assendelft GB, Greaves DR and Kollias G. . 1987 Cell 51: 975–985.

  • Hartl P and Lipp M. . 1987 Mol. Cell Biol. 7: 2037–2045.

  • Hayday AC, Gillies SD, Saito H, Wood C, Wimann K, Hayward WS and Tonegawa S. . 1984 Nature 307: 334–340.

  • Hollis GF, Mitchell KF, Battey J, Potter H, Taub R, Lenoir GM and Leder P. . 1984 Nature 307: 752–755.

  • Hörtnagel K, Mautner J, Strobl L, Wolf D, Christoph B, Geltinger C and Polack A. . 1995 Oncogene 10: 1393–1401.

  • Hug B, Moon A and Ley T. . 1992 Nucleic Acid Res. 20: 5771–5778.

  • Joos S, Haluska FG, Falk MH, Henglein B, Hameister B, Croce CM and Bornkamm GW. . 1992 Cancer Res. 52: 6547–6552.

  • Klehr D, Maass K and Bode J. . 1991 Biochemistry 30: 1264–1270.

  • Korsmeyer SJ. . 1992 Annu. Rev. Immunol. 10: 785–807.

  • Lee DY, Hayes JJ, Pruss D and Wolffe AP. . 1993 Cell 72: 73–84.

  • Look T. . 1997 Science 278: 1059–1064.

  • Madisen L and Groudine M. . 1994 Genes Dev. 8: 2212–2226.

  • Magrath I. . 1990 Adv. Cancer Res. 55: 134–270.

  • Mautner J, Joos S, Werner T, Eick D, Bornkamm GW and Polack A. . 1995 Nucleic Acid Res. 23: 72–80.

  • Mautner J, Behrends U, Hörtnagel K, Brielmeier M, Hammerschmidt W, Strobl L, Bornkamm GW and Polack A. . 1996 Oncogene 12: 1299–1307.

  • Nowell PC and Hungerford DA. . 1960 Science 132: 1497.

  • Nowell PC and Croce CM and Philip Levine Award Lecture. . 1990 Am. J. Clin. Pathol. 94: 229–237.

  • Polack A, Eick D, Koch E and Bornkamm GW. . 1987 EMBO J. 6: 2959–2964.

  • Polack A, Strobl L, Feederle R, Schweizer M, Koch E and Bornkamm GW. . 1991 Oncogene 6: 2033–2040.

  • Polack A, Feederle R, Klobeck G and Hörtnagel K. . 1993 EMBO J. 12: 3913–3920.

  • Pulvertaft RJV. . 1964 Lancet 1: 238–240.

  • Queen C and Stafford J. . 1984 Mol. Cell. Biol. 4: 1042–1049.

  • Rabbitts TH, Forster A, Baer R and Hamlyn PH. . 1983 Nature 306: 806–809.

  • Rabbitts TH. . 1994 Nature 372: 143–149.

  • Rottleb C, Bornkamm GW and Polack A. . 1995 Int. J. Cancer 62: 697–702.

  • Rottleb C, Bornkamm GW and Polack A. . 1996 Int. J. Cancer 67: 1–6.

  • Sambrook J, Fritsch EF and Maniatis T. . 1989 Cold Spring Harbor Laboratory Press.

  • Showe LC, Moore RC, Erikson J and Croce CM. . 1987 Proc. Natl. Acad. Sci. USA 84: 2824–2828.

  • Solomon E, Borrow J and Goddard AD. . 1991 Science 254: 1153–1160.

  • Stief A, Winter DM, Stratling WH and Sippel AE. . 1989 Nature 341: 341–345.

  • Strobl L, Kohlhuber F, Mautner J, Polack A and Eick D. . 1993 Oncogene 8: 1437–1447.

  • Sugden B, Marsh K and Yates J. . 1985 Mol. Cell Biol. 5: 410–413.

  • Zeidler R, Joos S, Delecluse H, Klobeck G, Vuillaume M, Lenoir GM, Bornkamm GW and Lipp M. . 1994 Genes Chrom. Cancer 9: 282–287.

  • Zimber-Strobl U, Strobl L, Kremmer E, Graesser F, Marschall G, Laux G and Bornkamm GW. . 1993 EMBO J. 12: 167–175.

Download references

Acknowledgements

We like to thank Raji Jayaraman, Eric Nisbet-Brown and Kenneth Cooke for helpful comments. This work was supportet by Die Deutsche Forschungsgemeinschaft, PO325/1-3 and Fonds der Chemischen Industrie. Correspondence should be sent to Armin Gerbitz.

Author information

Authors and Affiliations

  1. Dana Farber Cancer Institute, Pediatric Oncology M630, 44 Binney St., Boston, 02115, Massachusetts, USA

    A Gerbitz

  2. Department of Oncology, Johns Hopkins University, School of Medicine, Ross Building, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA

    J Mautner

  3. GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für klinische Molekularbiologie und Tumorgenetik, Marchioninistr. 25, München, 81377, Germany

    C Geltinger, B Christoph, A Polack & G W Bornkamm

  4. Ludwig-Maximilians-Universität München, Institut für Genetik, Goethestr. 29, München, 80336, Germany

    K Hörtnagel

  5. Adolf Butenandt Institut für Physiologische Chemie, Schillerstr. 44, München, 80336, Germany

    H Asenbauer & G Klobeck

Authors
  1. A Gerbitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Mautner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Geltinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Hörtnagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Christoph
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Asenbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Klobeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Polack
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G W Bornkamm
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerbitz, A., Mautner, J., Geltinger, C. et al. Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma. Oncogene 18, 1745–1753 (1999). https://doi.org/10.1038/sj.onc.1202468

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202468

Keywords

This article is cited by

Search

Advanced search

Quick links