來(lái)自加州大學(xué)圣地亞哥分校醫(yī)學(xué)院,，韓國(guó)西江大學(xué)（Sogang University）的研究人員發(fā)現(xiàn)了染色體易位與癌癥之間的相互關(guān)系的一個(gè)重要機(jī)制,，為進(jìn)一步研究腫瘤中染色體易位提供了重要依據(jù),。這一研究成果公布在Cell雜志上,。
染色體易位（chromosome translocation）是一種異?，F(xiàn)象,，主要有兩種類型：相互(reciprocal)易位和羅伯遜(Robert-sonian)易位,。染色體易位導(dǎo)致原來(lái)基因間連鎖關(guān)系的改變,，使本來(lái)在不同染色體上的基因由于染色體易位而處在相互鄰接的位置上,，特別是染色體斷端和重接位置上的基因，這會(huì)產(chǎn)生明顯的表型效應(yīng),。
這種現(xiàn)象是白血病,，淋巴瘤出現(xiàn)的一個(gè)標(biāo)志，也是其它實(shí)體腫瘤中常見(jiàn)的一種表征,，因此也吸引了許多科學(xué)家的興趣,，但是至今位置，癌癥染色體易位的具體機(jī)制還并不清楚,。
在這篇文章中,，研究人員通過(guò)建立了一個(gè)模擬細(xì)胞模型——能模擬在沒(méi)有增殖選擇（proliferation selection）的情況下，染色體易位事件發(fā)生的相對(duì)頻率,，發(fā)現(xiàn)了核受體依賴性腫瘤細(xì)胞染色體易位的機(jī)制,。
研究人員開(kāi)啟內(nèi)部和相互染色體易位后，雄激素受體（AR）發(fā)生內(nèi)源性結(jié)合,，這時(shí)由于AR和遺傳毒性應(yīng)激的誘導(dǎo),，催化了兩種類型的酶的活性，從而促使易位位點(diǎn)發(fā)生位點(diǎn)特異性DNA雙鏈斷裂（DSBs）,，這兩種酶分別是活化誘導(dǎo)胞嘧啶核苷脫氨酶,，和LINE-1重復(fù)編碼ORF2酶切反應(yīng)。
這些研究數(shù)據(jù)表明由配基核受體和遺傳毒性應(yīng)激啟動(dòng)的兩條平行途徑的交接點(diǎn),，是非隨機(jī)腫瘤染色體易位,，這也許在許多腫瘤和病理過(guò)程中都存在。
染色體易位的一個(gè)有關(guān)爭(zhēng)論是熊貓起源的爭(zhēng)論,，美國(guó)國(guó)家癌癥研究所的WilliamG.Nash采用染色體分帶技術(shù)對(duì)大熊貓和熊的染色體帶型進(jìn)行分析比較發(fā)現(xiàn)大熊貓的1號(hào)染色體可能是熊的2,，3號(hào)染色體羅伯遜易位的產(chǎn)物；同樣2號(hào)染色體與熊的1,，9號(hào)染色體同源,，3號(hào)染色體與熊的6，16號(hào)染色體同源從而得出最后的分類建議,，大熊貓與熊科中的熊有親緣關(guān)系,，小熊貓與浣熊科的浣熊有親緣關(guān)系,，將它的各自主為亞科。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
