Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma.
The pathogenesis of multiple myeloma (MM), an incurable tumour causing the deregulated proliferation of terminally differentiated B cells, is unknown. Chromosomal translocations (14q1) affecting band 14q32 and unidentified partner chromosomes are common in this tumour, suggesting that they may cause the activation of novel oncogenes. By cloning the chromosomal breakpoints in an MM cell line, we show that the 14q+ translocation represents a t(6;14)x(p25;q32) and that this aberration is recurrent in MM, as it was found in two of eleven MM cell lines. The translocation juxtaposes the immunoglobulin heavy-chain (IgH) locus to MUM1 (multiple myeloma oncogene 1)/IRF4 gene, a member of the interferon regulatory factor (IRF) family known to be active in the control of B-cell proliferation and differentiation. As a result, the MUM1/IRF4 gene is overexpressed--an event that may contribute to tumorigenesis, a MUM1/IRF4 has oncogenic activity in vitro. These findings identify a novel genetic alteration associated with MM, with implications for the pathogenesis and diagnostics of this tumour.
Iida
S
S
Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Rao
P H
PH
Butler
M
M
Corradini
P
P
Boccadoro
M
M
Klein
B
B
Chaganti
R S
RS
Dalla-Favera
R
R
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D051381:Rats; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains