Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma
Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma
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DOI：
10.1073/pnas.93.24.13931
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发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Kuehl, WM
中科院分区：
文献类型：
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作者：
Bergsagel, PL;Chesi, M;Kuehl, WM
在多发性骨髓瘤中，核型。14 q32易位已被确定在一个可变的频率（10-60%，在不同的研究）。在大多数情况下，伴侣染色体尚未确定（14 q+），在其余情况下，涉及多种染色体伴侣，其中11 q13是最常见的。我们开发了一个全面的Southern印迹分析，以确定和区分不同类型的免疫球蛋白重链（IgH）开关重组事件。不合法的开关重组片段（定义为仅包含一个开关区域的序列）是进入IgH开关区域的易位事件的潜在标志物，并在21个骨髓瘤细胞系中的15个中鉴定，包括8个核型分析的细胞系中的7个，这些细胞系没有检测到14 q32易位。从分析的所有9个细胞系或肿瘤样品中，进一步证实克隆的非法开关重组片段是IgH开关易位断点。在这些病例中的三例中，易位断裂点显示存在于原发性肿瘤中。这些易位断点涉及六个染色体位点：4p16.3（两个系和一个肿瘤）; 6; 8q24.13; 11q13.3（三个系）; 16q23.1;和21q22.1。我们认为IgH基因座的易位（i）是频繁的（核型14 q32易位和/或非法开关重组片段存在于原发性肿瘤样品和我们分析的21个细胞系中的19个中）;（ii）主要发生在开关区域;和（iii）涉及多样但非随机的阵列（即，通常为11 q13或4p 16）。这似乎是多发性骨髓瘤中最常见的遗传异常。
In multiple myeloma, karyotypic. 14q32 translocations have been identified at a variable frequency (10-60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the most common. We developed a comprehensive Southern blot assay to identify and distinguish different kinds of immunoglobulin heavy chain (IgH) switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only one switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma sell lines, including seven of eight karyotyped lines that have no detectable 14q32 translocation. From all nine lines or tumor samples analyzed Further, cloned illegitimate switch recombination fragments were confirmed to be IgH switch translocation breakpoints. In three of these cases, the translocation breakpoint was shown to be present in the primary tumor. These translocation breakpoints involve six chromosomal loci: 4p16.3 (two lines and the one tumor); 6; 8q24.13; 11q13.3 (in three lines); 16q23.1; and 21q22.1. We suggest that translocations into the IgH locus (i) are frequent (karyotypic 14q32 translocations and/or illegitimate switch recombination fragments are present in primary tumor samples and in 19 of 21 lines that we have analyzed); (ii) occur mainly in switch regions; and (iii) involve a diverse but nonrandom array (i.e., frequently 11q13 or 4p16) of chromosomal partners. This appears to be the most frequent genetic abnormality in multiple myeloma.