对4位慢性淋巴细胞性白血病患者的基因组进行分析，发现了4个突变基因（即NOTCH1、MYD88、XPO1 和 KLHL6），同时在300位以上的患者进行了验证。据认为，NOTCH1、 MYD88 和 XPO1突变常导致该型白血病的临床发病。有证据表明，NOTCH1 和 MYD88突变是白血病发病的激发因素，因此凸显了这2个基因成为潜在的治疗目标。
从白血病患者基因组中比对出突变基因
生物探索推荐英文摘要
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
Abstract: Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1, 2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3, 4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
