Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines.
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.
Chesi
M
M
National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD, 20889-5105, USA.
Bergsagel
P L
PL
Brents
L A
LA
Smith
C M
CM
Gerhard
D S
DS
Kuehl
W M
WM
D001483:Base Sequence; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005812:Genes, Switch; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009194:Myeloma Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D016213:Cyclins; D004273:DNA, Neoplasm; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D009194:Myeloma Proteins; D015513:Oncogene Proteins; D019938:Cyclin D1; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases