Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia
Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia
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DOI：
10.1111/bjh.12539
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发表时间：
2013-11-01
影响因子：
6.5
通讯作者：
Zenz, Thorsten
中科院分区：
文献类型：
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作者：
Jethwa, Alexander;Huellein, Jennifer;Zenz, Thorsten
复发性基因突变有助于慢性淋巴细胞白血病（CLL）的发病机制。我们开发了下一代测序（NGS）平台，以确定两个独立CLL队列的遗传特征、肿瘤内异质性和克隆结构。TP53、SF3B1和NOTCH 1突变频率最高（16.3%、16.9%、10.7%）。我们发现67.5%的癌症共有基因突变的CLL病例存在亚克隆突变的证据。我们观察了亚克隆的选择，并发现了CLL中会聚突变的初步证据。我们的数据表明，（亚）克隆结构的评估可能需要整合到CLL的突变谱分析。
Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.