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 mantlecell 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 lgH switch recombination, whereas mantle-cell lymphoma cells generally have not.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Blotting, Southern
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Chromosomes, Human, Pair 11 / genetics*
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Chromosomes, Human, Pair 14 / genetics*
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Cyclin D1
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Cyclins / genetics*
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DNA Nucleotidyltransferases / metabolism
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DNA, Neoplasm / genetics
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Gene Expression Regulation, Neoplastic*
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Genes, Switch*
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Humans
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Immunoglobulin Class Switching / genetics*
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Immunoglobulin G / genetics*
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Immunoglobulin Heavy Chains / genetics*
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Lymphoma, B-Cell / genetics
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Molecular Sequence Data
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Multiple Myeloma / genetics*
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Multiple Myeloma / pathology
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Myeloma Proteins / genetics*
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Oncogene Proteins / genetics*
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Recombination, Genetic
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Translocation, Genetic*
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VDJ Recombinases
Substances
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Cyclins
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DNA, Neoplasm
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Myeloma Proteins
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Oncogene Proteins
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Cyclin D1
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DNA Nucleotidyltransferases
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VDJ Recombinases
Associated data
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GENBANK/S82667
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GENBANK/S82668
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GENBANK/U73664
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GENBANK/U73665
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GENBANK/U73666
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GENBANK/U73667