Watanabe Yoshihisa, Ikemura Toshimichi, Sugimura Haruhiko
First Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
Genomics. 2004 Nov;84(5):796-805. doi: 10.1016/j.ygeno.2004.08.001.
Amplicons are frequently found in human tumor genomes, but the mechanism of their generation is still poorly understood. We previously measured the replication timing of the genes along the entire length of human chromosomes 11q and 21q and found that many "disease-related" genes are located in timing-transition regions. In this study, further scrutiny of the updated replication-timing map of human chromosome 11q revealed that both amplicons on human chromosomal bands 11q13 and 11q22 are located in the early/late-switch regions of replication timing in two human cell lines (THP-1 and Jurkat). Moreover, examination of synteny in the human and mouse genomes revealed that synteny breakage in both genomes occurred primarily at the early/late-switch regions of replication timing that we had identified. In conclusion, we found that the early/late-switch regions of replication timing coincided with "unstable" regions of the genome.
扩增子在人类肿瘤基因组中经常被发现，但其产生机制仍知之甚少。我们之前测量了人类11号染色体和21号染色体全长上基因的复制时间，发现许多“疾病相关”基因位于时间转换区域。在本研究中，对更新后的人类11号染色体复制时间图谱的进一步仔细研究表明，人类染色体带11q13和11q22上的两个扩增子在两个人类细胞系（THP-1和Jurkat）中均位于复制时间的早期/晚期转换区域。此外，对人类和小鼠基因组的同源性检查发现，两个基因组中的同源性断裂主要发生在我们所确定的复制时间的早期/晚期转换区域。总之，我们发现复制时间的早期/晚期转换区域与基因组的“不稳定”区域重合。
