Meaburn Karen J, Misteli Tom, Soutoglou Evi
National Cancer Institute, NIH, Bethesda, MD 20892, United States.
Semin Cancer Biol. 2007 Feb;17(1):80-90. doi: 10.1016/j.semcancer.2006.10.008. Epub 2006 Oct 26.
Chromosomal translocations and genomic instability are universal hallmarks of tumor cells. While the molecular mechanisms leading to the formation of translocations are rapidly being elucidated, a cell biological understanding of how chromosomes undergo translocations in the context of the cell nucleus in vivo is largely lacking. The recent realization that genomes are non-randomly arranged within the nuclear space has profound consequences for mechanisms of chromosome translocations. We review here the emerging principles of spatial genome organization and discuss the implications of non-random spatial genome organization for the genesis and specificity of cancerous chromosomal translocations.
染色体易位和基因组不稳定是肿瘤细胞的普遍特征。虽然导致易位形成的分子机制正在迅速得到阐明,但在很大程度上缺乏对染色体在体内细胞核环境中如何发生易位的细胞生物学理解。最近认识到基因组在核空间内是非随机排列的,这对染色体易位机制具有深远影响。我们在此回顾空间基因组组织的新兴原理,并讨论非随机空间基因组组织对癌性染色体易位的发生及其特异性的影响。