The recurrent translocation t(14;20)(q32;q12) in multiple myeloma results in aberrant expression of MAFB: a molecular and genetic analysis of the chromosomal breakpoint.
Chromosomal translocations of the immunoglobulin heavy chain (IgH) gene region at 14q32 are regularly involved in B lymphoid malignancies; they may initiate transformation either by deregulation of existing (proto) oncogenes or creation of new hybrid genes with transforming properties. Previously, we reported a reciprocal novel translocation, t(14;20)(q32;q12), found in the myeloma cell line UM3. In this cell line, the t(14;20) is the only translocation involving the IgH locus. Using double colour immunofluorescence in situ hybridization, the t(14;20) was also found in the diagnostic bone marrow sample, excluding a possible in vitro artefact. We also have found this recurrent t(14;20) in four other cell lines and in additional patient material. We cloned the regions containing the breakpoints in the der(14) and der(20) chromosomes from UM3, and analysed ectopic mRNA expression of genes in the breakpoint regions of both derivative chromosomes. Ectopic gene expression was observed for the transcription factor MAFB in der(14). The breakpoint scatter in the five cell lines with a t(14;20)--all expressing MAFB--is comprised within a region of 0.8 Mb. Provisional data indicate that this t(14;20) is associated with an adverse prognosis. Aberrant expression of MAFB may be involved in the oncogenic transformation of myeloma cells that harbour the t(14;20).
Boersma-Vreugdenhil
Gienke R
GR
Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Kuipers
Jeroen
J
Van Stralen
Esther
E
Peeters
Ton
T
Michaux
Lucienne
L
Hagemeijer
Anne
A
Pearson
Peter L
PL
Clevers
Hans C
HC
Bast
Bert J E G
BJ
D000368:Aged; D030161:Avian Proteins; D015152:Blotting, Northern / Q000379:methods; D045744:Cell Line, Tumor; D002883:Chromosomes, Human, Pair 14; D002890:Chromosomes, Human, Pair 20; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051258:MafB Transcription Factor; D009101:Multiple Myeloma / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D030161:Avian Proteins; D004268:DNA-Binding Proteins; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D015513:Oncogene Proteins; D014157:Transcription Factors