Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Blood Cancer J. 2019 Aug 6;9(8):60. doi: 10.1038/s41408-019-0221-9.
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.
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。我们发现编码和非编码区域分别由不同的单核苷酸变异（SNV）突变特征以及五个新出现的结构重排特征主导。反映不同主要突变过程——衰老、DNA 修复缺陷和载脂蛋白 B 编辑复合物（APOBEC）/激活诱导脱氨酶活性的突变特征表征了 MM。这些突变特征显示出亚组特异性的证据——与 MAF 易位 t(14;16)和 t(14;20) MM 相关的 APOBEC 归因的特征；可能与 t(11;14)和 t(4;14)相关的 DNA 修复缺陷；以及与超二倍体相关的衰老。与 APOBEC 相关的突变特征与既定的预后标志物无关，似乎与预测高危 MM 有关。
