来自加州大学圣地亚哥分校医学院，韩国西江大学（Sogang University）的研究人员发现了染色体易位与癌症之间的相互关系的一个重要机制，为进一步研究肿瘤中染色体易位提供了重要依据。这一研究成果公布在Cell杂志上。
染色体易位（chromosome translocation）是一种异常现象，主要有两种类型：相互(reciprocal)易位和罗伯逊(Robert-sonian)易位。染色体易位导致原来基因间连锁关系的改变，使本来在不同染色体上的基因由于染色体易位而处在相互邻接的位置上，特别是染色体断端和重接位置上的基因，这会产生明显的表型效应。
这种现象是白血病，淋巴瘤出现的一个标志，也是其它实体肿瘤中常见的一种表征，因此也吸引了许多科学家的兴趣，但是至今位置，癌症染色体易位的具体机制还并不清楚。
在这篇文章中，研究人员通过建立了一个模拟细胞模型——能模拟在没有增殖选择（proliferation selection）的情况下，染色体易位事件发生的相对频率，发现了核受体依赖性肿瘤细胞染色体易位的机制。
研究人员开启内部和相互染色体易位后，雄激素受体（AR）发生内源性结合，这时由于AR和遗传毒性应激的诱导，催化了两种类型的酶的活性，从而促使易位位点发生位点特异性DNA双链断裂（DSBs），这两种酶分别是活化诱导胞嘧啶核苷脱氨酶，和LINE-1重复编码ORF2酶切反应。
这些研究数据表明由配基核受体和遗传毒性应激启动的两条平行途径的交接点，是非随机肿瘤染色体易位，这也许在许多肿瘤和病理过程中都存在。
染色体易位的一个有关争论是熊猫起源的争论，美国国家癌症研究所的WilliamG.Nash采用染色体分带技术对大熊猫和熊的染色体带型进行分析比较发现大熊猫的1号染色体可能是熊的2，3号染色体罗伯逊易位的产物；同样2号染色体与熊的1，9号染色体同源，3号染色体与熊的6，16号染色体同源从而得出最后的分类建议，大熊猫与熊科中的熊有亲缘关系，小熊猫与浣熊科的浣熊有亲缘关系，将它的各自主为亚科。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 139, Issue 6, 1069-1083, 03 December 2009 doi:10.1016/j.cell.2009.11.030
Nuclear Receptor-Induced Chromosomal Proximity and DNA Breaks Underlie Specific Translocations in Cancer
Chunru Lin1, 6, Liuqing Yang1, 6, Bogdan Tanasa1, Kasey Hutt2, Bong-gun Ju1, 5, Kenny Ohgi1, Jie Zhang1, David W. Rose3, Xiang-Dong Fu4, Christopher K. Glass4 and Michael G. Rosenfeld1, 3, ,
1 Howard Hughes Medical Institute, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA
2 Bioinformatics Graduate Program, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA
3 Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA
4 Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA
5 Department of Life Science, Sogang University, Seoul 121-742, Korea
Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear in solid tumors, but the underlying mechanism remains elusive. By establishing a cellular model that mimics the relative frequency of authentic translocation events without proliferation selection, we report mechanisms of nuclear receptor-dependent tumor translocations. Intronic binding of liganded androgen receptor (AR) first juxtaposes translocation loci by triggering intra- and interchromosomal interactions. AR then promotes site-specific DNA double-stranded breaks (DSBs) at translocation loci by recruiting two types of enzymatic activities induced by genotoxic stress and liganded AR, including activation-induced cytidine deaminase and the LINE-1 repeat-encoded ORF2 endonuclease. These enzymes synergistically generate site-selective DSBs at juxtaposed translocation loci that are ligated by nonhomologous end joining pathway for specific translocations. Our data suggest that the confluence of two parallel pathways initiated by liganded nuclear receptor and genotoxic stress underlies nonrandom tumor translocations, which may function in many types of tumors and pathological processes.
