Piccoli S P, Caimi P G, Cole M D
Nature. 1984;310(5975):327-30. doi: 10.1038/310327a0.
Many recent studies have shown that chromosomal translocation breakpoints frequently occur near cellular proto-oncogenes (reviewed in ref. 1). In both mouse plasmacytomas and Burkitt lymphomas, the c-myc oncogene becomes joined to an immunoglobulin heavy-chain gene in a head-to-head configuration. Within c-myc, the breaks frequently occur near the first exon-intron boundary, while within the immunoglobulin gene the breaks usually involve sequences directing heavy-chain switching. It has been assumed that the translocations represent abortive immunoglobulin switching events which have activated the c-myc gene for a role in tumour formation. However, sequence analysis of the c-myc gene does not reveal any apparent similarity to the immunoglobulin switch signals. With these results in mind, we have determined the precise breakpoints within c-myc for two plasmacytoma lines in order to search for any common features that may shed some light on the mechanism of chromosomal translocation. We report here that the tetranucleotide sequence GAGG occurs close to the breakpoint in five out of six translocations, and so may be a sequence recognized by either the enzymes that catalyse immunoglobulin heavy-chain switching, or some other DNA-cleaving activity.
许多近期研究表明，染色体易位断点经常出现在细胞原癌基因附近（参考文献1中有综述）。在小鼠浆细胞瘤和伯基特淋巴瘤中，c-myc原癌基因都以头对头的形式与免疫球蛋白重链基因相连。在c-myc基因内部，断点经常出现在第一个外显子-内含子边界附近，而在免疫球蛋白基因内部，断点通常涉及指导重链类别转换的序列。人们认为这种易位代表了失败的免疫球蛋白类别转换事件，这些事件激活了c-myc基因，使其在肿瘤形成中发挥作用。然而，对c-myc基因的序列分析并未揭示其与免疫球蛋白类别转换信号有任何明显的相似性。考虑到这些结果，我们确定了两个浆细胞瘤细胞系中c-myc基因内的精确断点，以便寻找可能有助于阐明染色体易位机制的任何共同特征。我们在此报告，在六次易位中的五次中，四核苷酸序列GAGG出现在断点附近，因此它可能是被催化免疫球蛋白重链类别转换的酶或其他一些DNA切割活性所识别的序列。
