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摘要 : 对来自538个慢性淋巴性白血病(CLL)患者的样本(包括作为一项前瞻性临床试验的一部分所收集的来自278个患者的样本)所做的全外显子组测序(WES)的结果

来自“国际癌症基因组联盟”的这篇论文,报告了用来表征500多位患者慢性淋巴性白血病及其前兆的若干种基因组学方法所获得的结果。除了增加了在基因组的编码部分所见到的慢性淋巴性白血病的驱动改变(driver alterations)的数量外,这项研究还在非编码区域(包括NOTCH1的3′ UTR区域)识别出了新的频发突变(这些突变造成异常剪接事件、NOTCH1活性的增强和更具侵略性的疾病),也在一个增强子中识别出了导致“B-细胞特异性转录因子” PAX5的表达程度降低的突变。 



Mutations driving CLL and their evolution in progression and relapse


Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.

来源: Nature 浏览次数:0


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