Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway.
Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway.
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DOI：
10.1038/s41408-023-00783-0
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发表时间：
2023-01-20
影响因子：
12.8
通讯作者：
Walker, Brian A.
中科院分区：
文献类型：
--
作者：
Liu, Enze;Becker, Nathan;Sudha, Parvathi;Dong, Chuanpeng;Liu, Yunlong;Keats, Jonathan;Morgan, Gareth;Walker, Brian A.
选择性剪接在肿瘤的发生和增殖中起着关键作用。然而，其模式和致病作用尚未在多发性骨髓瘤或其亚型中进行系统分析。对598例新诊断的骨髓瘤患者进行全面基因组注释的选择性剪接谱鉴定出原发性易位、1q扩增和DIS3事件比没有的事件具有更多的差异剪接事件。剪接水平与剪接因子的表达相关。此外，非同源末端连接途径是与剪接频率以及增加的结构变体数量高度相关的独立因素。因此，我们确定了一个轴的高风险疾病，包括表达的非同源末端连接途径，增加结构变异，并增加选择性剪接连接在一起。这表明骨髓瘤中DNA损伤反应和替代RNA加工的联合致病作用。
Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotation identified primary translocations, 1q amplification, and DIS3 events to have more differentially spliced events than those without. Splicing levels were correlated with expression of splicing factors. Moreover, the non-homologous end joining pathway was an independent factor that was highly associated with splicing frequency as well as an increased number of structural variants. We therefore identify an axis of high-risk disease encompassing expression of the non-homologous end joining pathway, increase structural variants, and increased alternative splicing that are linked together. This indicates a joint pathogenic role for DNA damage response and alternative RNA processing in myeloma.
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影响因子：
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通讯作者：
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