Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Nat Commun. 2021 Aug 27;12(1):5172. doi: 10.1038/s41467-021-25469-8.
Chromothripsis is detectable in 20-30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.
染色体重排可在 20-30%的新发多发性骨髓瘤（NDMM）患者中检测到，并且正在成为新的独立不良预后因素。在这项研究中，我们使用全基因组测序（WGS）对 752 名 NDMM 患者进行检测，以研究拷贝数（CN）特征与染色体重排的关系，并显示它们高度相关。CN 特征高度预测染色体重排的存在（AUC=0.90），并可用于识别其不良预后影响。CN 特征预测染色体重排存在的能力在由 235 例血液系统癌症（AUC=0.97）和 34 例 NDMM 的独立系列组成的 WGS 验证系列中得到了证实（AUC=0.87）。我们表明，CN 特征也可以从全外显子组数据（WES）中得出，并且使用相同系列的 677 例 NDMM，我们能够预测染色体重排的存在（AUC=0.82）及其不良预后影响。CN 特征是一种灵活的工具，可用于识别染色体重排的存在，适用于 WES 和 WGS 数据。
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