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Long-range oncogenic activation of Igh–c-myc translocations by the Igh 3′ regulatory region

Author

Listed:
  • Monica Gostissa

    (Howard Hughes Medical Institute,
    The Children’s Hospital,
    Immune Disease Institute,
    Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Catherine T. Yan

    (Howard Hughes Medical Institute,
    The Children’s Hospital,
    Immune Disease Institute,
    Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Julia M. Bianco

    (Howard Hughes Medical Institute,
    The Children’s Hospital,
    Immune Disease Institute,
    Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Michel Cogné

    (Centre National de la Recherche Scientifique
    Université de Limoges, UMR 6101, Faculté de Médecine, Limoges France)

  • Eric Pinaud

    (Centre National de la Recherche Scientifique
    Université de Limoges, UMR 6101, Faculté de Médecine, Limoges France)

  • Frederick W. Alt

    (Howard Hughes Medical Institute,
    The Children’s Hospital,
    Immune Disease Institute,
    Harvard Medical School, Boston, Massachusetts 02115, USA)

Abstract

Immunoglobulin heavy chain locus activates c-myc proto-oncogene Lymphomas often possess a translocation that juxtaposes the c-myc proto-oncogene and the immunoglobulin heavy chain (IgH) locus. Two hundred kilobases downstream of the Igh constant region exons is a regulatory locus, Igh3′ RR, which has been proposed to deregulate c-myc expression. To definitively show that Igh3′ RR has a role in oncogenesis, Alt and colleagues have inactivated it in two mouse models carrying Igh-c-myc translocations. These data show that while Igh3′ RR is dispensable for lymphomas from progenitor B cells that have only undergone V(D)J recombination, it is required to activate c-myc in peripheral B cells that have also undergone class switch recombination. Thus, Igh3′ RR acts at a distance in a developmental-specific manner to activate c-myc.

Suggested Citation

  • Monica Gostissa & Catherine T. Yan & Julia M. Bianco & Michel Cogné & Eric Pinaud & Frederick W. Alt, 2009. "Long-range oncogenic activation of Igh–c-myc translocations by the Igh 3′ regulatory region," Nature, Nature, vol. 462(7274), pages 803-807, December.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7274:d:10.1038_nature08633
    DOI: 10.1038/nature08633
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