Mutational processes contributing to the development of multiple myeloma
Mutational processes contributing to the development of multiple myeloma
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DOI：
10.1038/s41408-019-0221-9
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发表时间：
2019-08-06
影响因子：
12.8
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
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作者：
Hoang, Phuc H.;Cornish, Alex J.;Houlston, Richard S.
为了深入了解多发性骨髓瘤 (MM) 肿瘤发生，我们分析了 CoMMpass 研究中的 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由不同的单核苷酸变异（SNV）突变特征以及五个从头结构重排特征差异主导。反映不同原理突变过程的突变特征——衰老、有缺陷的 DNA 修复和载脂蛋白 B 编辑复合物 (APOBEC)/激活诱导的脱氨酶活性是 MM 的特征。这些突变特征显示了与 MAF 易位 t(14;16) 和 t(14;20) MM 相关的亚组特异性 - APOBEC 归因特征的证据； t(11;14) 和 t(4;14) 可能存在 DNA 修复缺陷；和超二倍体老化。与 APOBEC 相关的突变特征与已建立的预后标志物无关，并且似乎与预测高风险 MM 相关。
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 processe-saging, 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.