文章：

导致多发性骨髓瘤发展的突变过程

Mutational processes contributing to the development of multiple myeloma

原文发布日期：2019-08-06

DOI: 10.1038/s41408-019-0221-9

类型: Article

开放获取: 是

英文摘要：

To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes—aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity—characterize MM. These mutational signatures show evidence of subgroup specificity—APOBEC-attributed signatures associated with MAF translocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM.
 

摘要翻译： 

为了深入了解多发性骨髓瘤（MM）的肿瘤发生机制，我们分析了CoMMpass研究中874个全外显子组和850个全基因组数据中的突变特征。我们发现编码区和非编码区分别由不同的单核苷酸变异（SNV）突变特征主导，并识别出五种新发结构重排特征。反映不同主要突变过程——衰老、DNA修复缺陷以及载脂蛋白B编辑复合物（APOBEC）/激活诱导脱氨酶活性——的突变特征构成了MM的典型特征。这些突变特征显示出亚群特异性：APOBEC相关特征与MAF易位t(14;16)和t(14;20)型MM相关；潜在DNA修复缺陷与t(11;14)和t(4;14)相关；衰老特征与超二倍体相关。除APOBEC相关特征外，其他突变特征独立于已建立的预后标志物，并似乎对预测高危MM具有重要价值。

原文链接：

Mutational processes contributing to the development of multiple myeloma