Pear W S, Nelson S F, Axelson H, Wahlström G, Bazin H, Klein G, Sümegi J
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Oncogene. 1988 May;2(5):499-507.
Our previous studies of spontaneously arising rat immunocytomas of the Lou/Wsl strain have shown that Ig switch regions are frequently the targets for c-myc recombination. In several tumors, however, we were unable to show recombination of the c-myc with Ig switch regions. We have cloned the rearranged c-myc fragments from 2 of these tumors, IR209 and IR223, and found that the c-myc recombines with a LINE region in the IR209 and with intron 1 of the epsilon locus in the IR223. Although switch regions are not found at the breakpoints, the sequences at the breakpoints share limited homology with Ig switch recognition sequences. This suggests that the switch recombinase enzymes are able to recognize sequences in addition to the defined switch recombination sites. At the same time, both the LINE and epsilon intron 1 sequences are located within the Ig cluster, providing further evidence for the selection of c-myc activation by Ig sequences in the pathogenesis of rat immunocytoma, mouse plasmacytoma, and Burkitt's lymphoma.
我们之前对Lou/Wsl品系自发产生的大鼠免疫细胞瘤的研究表明，Ig转换区经常是c-myc重组的靶点。然而，在一些肿瘤中，我们未能显示c-myc与Ig转换区的重组。我们从其中2个肿瘤IR209和IR223中克隆了重排的c-myc片段，发现c-myc在IR209中与一个LINE区域重组，在IR223中与ε基因座的内含子1重组。尽管在断点处未发现转换区，但断点处的序列与Ig转换识别序列有有限的同源性。这表明转换重组酶除了能识别已定义的转换重组位点外，还能识别其他序列。同时，LINE和ε内含子1序列都位于Ig簇内，为在大鼠免疫细胞瘤、小鼠浆细胞瘤和伯基特淋巴瘤的发病机制中Ig序列选择激活c-myc提供了进一步的证据。
