Sekido Y, Takahashi T, Mäkelä T P, Obata Y, Ueda R, Hida T, Hibi K, Shimokata K, Alitalo K, Takahashi T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Mol Cell Biol. 1992 Apr;12(4):1747-54. doi: 10.1128/mcb.12.4.1747-1754.1992.
The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N-myc. A new mechanism of L-myc activation which results from the production of rlf-L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts.
L-myc基因最初是从人小细胞肺癌（SCLC）细胞系中分离出来的，基于其与c-myc和N-myc的扩增及序列相似性。最近报道了一种由rlf-L-myc融合蛋白产生导致L-myc激活的新机制。基于我们早期在一个SCLC细胞系ACC-LC-49中观察到涉及扩增的L-myc的重排，我们决定详细研究这种重排以及另外五个SCLC细胞系中L-myc扩增单元的结构。我们在此报告鉴定了一个新的基因组区域，称为jal，它与rlf不同，在包含L-myc的区域的DNA扩增过程中与L-myc并列并一起扩增。使用脉冲场凝胶电泳的长程分析表明，扩增的L-myc基因座参与了与jal和/或rlf的高度复杂的染色体内重排。我们的结果还表明，rlf内含子1和L-myc紧邻上游区域同时存在重排可能是rlf-L-myc嵌合转录本表达所必需的。
