New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing
New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing
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DOI：
10.1371/journal.pone.0038158
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发表时间：
2012-06-01
期刊：
影响因子：
3.7
通讯作者：
Sanchez-Beato, Margarita
中科院分区：
文献类型：
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作者：
Domenech, Elena;Gomez-Lopez, Gonzalo;Sanchez-Beato, Margarita
慢性淋巴细胞白血病(CLL)是一种异质性疾病，没有明确的基因改变导致疾病的发生。有几条证据表明，B细胞受体(BCR)和辅助受体以及NFkB途径传递的刺激和生长信号是CLL中B细胞存活的驱动力。然而，导致这种激活的分子机制尚未确定。基于bcr激活可能依赖于bcr及相关通路的体细胞突变的假设，我们利用大规模平行测序技术对10例CLL患者的301个与bcr信号及相关通路相关的基因进行了完整的突变筛查。毛细管测序证实了编码区的4个突变基因(KRAS、SMARCA2、NFKBIE和PRKD3)。总之，这项研究发现了CLL中突变的新基因，所有这些基因都在进展性疾病的病例中，并证明了应用于选定的基因或感兴趣的途径的下一代测序技术是识别新的突变变化的强大工具。
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes.