文章：

多发性骨髓瘤中的可变剪接与非同源末端连接通路相关

Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway

原文发布日期：2023-01-20

DOI: 10.1038/s41408-023-00783-0

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

可变剪接在肿瘤发生与增殖过程中起着关键作用。然而，其在多发性骨髓瘤及其亚型中的模式和致病作用尚未得到系统分析。通过对598名新诊断且具有完整基因组注释的骨髓瘤患者进行可变剪接图谱分析，发现与未发生相关遗传事件的患者相比，存在原发性易位、1q扩增及DIS3突变的患者具有更多差异剪接事件。剪接水平与剪接因子的表达呈相关性。此外，非同源末端连接通路不仅是与剪接频率高度相关的独立因素，也与结构变异数量的增加有关。由此，我们揭示了一个高风险疾病轴心，该轴心将非同源末端连接通路的表达增强、结构变异增多以及可变剪接增加相互关联。这表明DNA损伤反应与可变RNA加工在多发性骨髓瘤中具有协同致病作用。

原文链接：

Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway