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

Monica Gostissa, Catherine T. Yan, Julia M. Bianco, Michel Cogné, Eric Pinaud and Frederick W. Alt ()
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Monica Gostissa: Howard Hughes Medical Institute,
Catherine T. Yan: Howard Hughes Medical Institute,
Julia M. Bianco: Howard Hughes Medical Institute,
Michel Cogné: Centre National de la Recherche Scientifique
Eric Pinaud: Centre National de la Recherche Scientifique
Frederick W. Alt: Howard Hughes Medical Institute,

Nature, 2009, vol. 462, issue 7274, 803-807

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.

Date: 2009
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DOI: 10.1038/nature08633

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