Boersma-Vreugdenhil Gienke R, Kuipers Jeroen, Van Stralen Esther, Peeters Ton, Michaux Lucienne, Hagemeijer Anne, Pearson Peter L, Clevers Hans C, Bast Bert J E G
Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Br J Haematol. 2004 Aug;126(3):355-63. doi: 10.1111/j.1365-2141.2004.05050.x.
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).
位于14q32的免疫球蛋白重链（IgH）基因区域的染色体易位经常与B淋巴细胞恶性肿瘤有关；它们可能通过使现有（原）癌基因失调或产生具有转化特性的新杂交基因来启动细胞转化。此前，我们报道了在骨髓瘤细胞系UM3中发现的一种相互性新型易位t(14;20)(q32;q12)。在该细胞系中，t(14;20)是涉及IgH基因座的唯一易位。使用双色免疫荧光原位杂交技术，在诊断性骨髓样本中也发现了t(14;20)，排除了可能的体外假象。我们还在其他四个细胞系和另外的患者材料中发现了这种复发性t(14;20)。我们从UM3中克隆了包含der(14)和der(20)染色体断点的区域，并分析了两个衍生染色体断点区域中基因的异位mRNA表达。在der(14)中观察到转录因子MAFB的异位基因表达。具有t(14;20)的五个细胞系（均表达MAFB）中的断点分散在0.8 Mb的区域内。初步数据表明，这种t(14;20)与不良预后相关。MAFB的异常表达可能参与了携带t(14;20)的骨髓瘤细胞的致癌转化。
