對不同患者體內(nèi)的癌細(xì)胞所做的全基因組分析顯示了廣泛的遺傳異質(zhì)性。現(xiàn)在,，兩個(gè)小組對“急性淋巴母細(xì)胞白血病”(ALL)患者進(jìn)行了全面分析,。Mel Greaves及其同事獲得了來自60位ETV6–RUNX1-陽性ALL患者的大量單細(xì)胞突變分布圖,，而John Dick及其同事則對BCR-ABL1-陽性ALL患者進(jìn)行了分析。兩個(gè)小組都推斷出了在疾病發(fā)展過程中不同亞克隆是如何形成的演化途徑,。轉(zhuǎn)移該疾病的白血病傳播細(xì)胞映照大體積腫瘤的基因變異,，從而為在基因?qū)用嫔狭私膺@些功能性亞組的異質(zhì)性提供了線索。這項(xiàng)工作對于以腫瘤,、特別是白血病傳播細(xì)胞為目標(biāo)的治療方法有參考意義,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09650
Genetic variegation of clonal architecture and propagating cells in leukaemia
Kristina Anderson,Christoph Lutz,Frederik W. van Delft,Caroline M. Bateman,Yanping Guo,Susan M. Colman,Helena Kempski,Anthony V. Moorman,Ian Titley,John Swansbury,Lyndal Kearney,Tariq Enver& Mel Greaves
Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6–RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or ‘driver’ copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγnull mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer.
