对不同患者体内的癌细胞所做的全基因组分析显示了广泛的遗传异质性。现在，两个小组对“急性淋巴母细胞白血病”(ALL)患者进行了全面分析。Mel Greaves及其同事获得了来自60位ETV6–RUNX1-阳性ALL患者的大量单细胞突变分布图，而John Dick及其同事则对BCR-ABL1-阳性ALL患者进行了分析。两个小组都推断出了在疾病发展过程中不同亚克隆是如何形成的演化途径。转移该疾病的白血病传播细胞映照大体积肿瘤的基因变异，从而为在基因层面上了解这些功能性亚组的异质性提供了线索。这项工作对于以肿瘤、特别是白血病传播细胞为目标的治疗方法有参考意义。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
