Pear W S, Ingvarsson S, Steffen D, Münke M, Francke U, Bazin H, Klein G, Sümegi J
Proc Natl Acad Sci U S A. 1986 Oct;83(19):7376-80. doi: 10.1073/pnas.83.19.7376.
Spontaneously arising immunocytomas in Lou/Wsl rats contain a consistent translocation between chromosomes 6 and 7. The c-myc gene has been localized to chromosome 7 and has been shown to be rearranged in the majority of the rat immunocytomas. We now report the cloning of the rearranged 11-kilobase EcoRI c-myc fragment from the IgE-secreting IR75 tumor. Sequence analysis revealed that the cytogenetically visible t(6;7) translocation must have involved several events in this tumor. One event has led to the juxtaposition of c-myc and the switch mu region, in a head-to-head orientation. The breakpoint is approximately 850 base pairs upstream from the proximal c-myc promoter on chromosome 7. This area is distinct from the more common mouse plasmacytoma- and Burkitt lymphoma-associated translocation breakpoints and also differs from the known murine retroviral insertion sites. A second rearrangement has led to the transposition of sequences upstream from the switch gamma 1 region to the c-myc-distant end of the switch mu region, tail-to-tail. This requires at least two events, including one inversion. In addition to showing that identical loci (c-myc, immunoglobulin) are juxtaposed via chromosomal translocations in three different tumors (Burkitt lymphoma, mouse plasmacytoma, and rat immunocytoma) in different species (human, mouse, and rat), the multiple rearrangements in IR75 and some other tumors emphasize the selective value of c-myc activation by an immunoglobulin locus in the tumorigenic process.
在Lou/Wsl大鼠中自发产生的免疫细胞瘤含有6号和7号染色体之间一致的易位。c-myc基因已定位到7号染色体，并且已证实在大多数大鼠免疫细胞瘤中发生了重排。我们现在报告从分泌IgE的IR75肿瘤中克隆重排的11千碱基EcoRI c-myc片段。序列分析表明，细胞遗传学上可见的t(6;7)易位在该肿瘤中必定涉及多个事件。一个事件导致c-myc与转换μ区以头对头的方向并列。断点位于7号染色体上近端c-myc启动子上游约850个碱基对处。该区域不同于更常见的小鼠浆细胞瘤和伯基特淋巴瘤相关的易位断点，也不同于已知的小鼠逆转录病毒插入位点。第二个重排导致转换γ1区上游的序列以尾对尾的方式转位到转换μ区的c-myc远端。这至少需要两个事件，包括一次倒位。除了表明在不同物种（人、小鼠和大鼠）的三种不同肿瘤（伯基特淋巴瘤、小鼠浆细胞瘤和大鼠免疫细胞瘤）中，相同的基因座（c-myc、免疫球蛋白）通过染色体易位并列外，IR75和其他一些肿瘤中的多重重排强调了在致瘤过程中免疫球蛋白基因座激活c-myc的选择性价值。
