腎臟腫瘤,，圖片來自維基共享資源,。
根據(jù)2012年3月8日發(fā)表在New England Journal of Medicine期刊上的一篇論文,，研究人員追蹤了腫瘤的進化樹,，從而發(fā)現(xiàn)腫瘤存在高度的遺傳異質(zhì)性,，這有助于闡明為何個人化癌癥治療可能不是有效的。單次活組織檢查(biopsy)將只能深入了解腫瘤內(nèi)一個位點的突變,，而有些突變導(dǎo)致腫瘤對不同治療方法產(chǎn)生不同反應(yīng)或預(yù)后結(jié)果,，但是這些突變可能潛藏在腫瘤其他位點，這可能能夠解釋為何抗腫瘤療法經(jīng)常是先能夠發(fā)揮抗腫瘤功能但是過一段時間后就失去療效,。
“我們在相當(dāng)長的一段時間內(nèi)認(rèn)為腫瘤是癌細(xì)胞拼湊出來的,，但是這是第一次我們能夠使用前沿的基因組測序技術(shù)來極其精細(xì)地描繪出一個腫瘤的遺傳全貌”，論文通訊作者和英國癌癥研究中心/倫敦研究所腫瘤遺傳學(xué)家Charles Swanton說,。
Swanton和他的同事們追蹤腫瘤基因組進化并研究人腎臟腫瘤的遺傳異常性,。研究人員在一個病人所患的原發(fā)性腎臟腫瘤的幾個位點及其幾個轉(zhuǎn)移瘤中進行活組織檢測，并發(fā)現(xiàn)鑒定出的突變當(dāng)中只有34%在病人所有樣品中都是一樣的,。隨后,，他們構(gòu)建出一個原發(fā)性腫瘤和一個轉(zhuǎn)移瘤的進化樹，結(jié)果表明一個癌細(xì)胞系在病人身上產(chǎn)生轉(zhuǎn)移瘤,，而另一個主要的癌細(xì)胞系支持原發(fā)性腫瘤生長,，這些暗示著基于原發(fā)性腫瘤的活組織檢測結(jié)果進行針對性治療可能并不能有效地治療轉(zhuǎn)移瘤,。Swanto說,，如果能夠發(fā)現(xiàn)哪些突變在腫瘤內(nèi)不同細(xì)胞之間以及在不同腫瘤之間是相同的，那么科學(xué)家可能能夠設(shè)計出一個更加全面的治療策略。(生物谷：towersimper編譯)
doi:10.1056/NEJMoa1113205
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Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Marco Gerlinge, Andrew J. Rowan, B.Sc., Stuart Horswell, M.Math., James Larkin, David Endesfelder, et al.
Pluripotency is a central, well-studied feature of embryonic development, but the role of pluripotent cell regulation in somatic tissue regeneration remains poorly understood. In planarians, regeneration of entire animals from tissue fragments is promoted by the activity of adult pluripotent stem cells (cNeoblasts). We utilized transcriptional profiling to identify planarian genes expressed in adult proliferating, regenerative cells (neoblasts). We also developed quantitative clonal analysis methods for expansion and differentiation of cNeoblast descendants that, together with RNAi, revealed gene roles in stem cell biology. Genes encoding two zinc finger proteins, Vasa, a LIM domain protein, Sox and Jun-like transcription factors, two candidate RNA-binding proteins, a Setd8-like protein, and PRC2 (Polycomb) were required for proliferative expansion and/or differentiation of cNeoblast-derived clones. These findings suggest that planarian stem cells utilize molecular mechanisms found in germ cells and other pluripotent cell types and identify genetic regulators of the planarian stem cell system.
