Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines

Abstract

Translocations involving the IgH locus at chromosomal locus 14q32.3 are a common event in many B-cell malignancies. The translocations, which generally occur into JH and switch regions, are mediated by errors in the two developmentally regulated, lymphocyte-specific pathways: VDJ- and switch- mediated recombination. Dysregulation of cyclin D1 by a t(11; 14)(q13;q32) translocation occurs in most cases of mantle-cell lymphoma and in approximately 30% of multiple myeloma (MM) tumors in which a 14q32 translocation can be detected. We show here that in two of three myeloma lines that overexpress cyclin D1, there is an 11;14 translocation into a gamma switch region, suggesting an error in switch recombination. By contrast, 11;14 translocations in mantle-cell lymphoma are invariably into or near a JH segment, suggesting an error in VDJ recombination. This is consistent with the fact that myeloma cells have undergone IgH switch recombination, whereas mantle-cell lymphoma cells generally have not.