In multiple myeloma, next generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here, we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number changes (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and IMiD-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.344.

中文翻译：

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对多发性骨髓瘤的基因组格局的分析突出了新的预后标志物和疾病亚组。

在多发性骨髓瘤中，下一代测序（NGS）扩展了我们对基因组病变的认识，并强调了肿瘤的动态和异质性组成。在这里，我们使用NGS表征了418例多发性骨髓瘤病例在诊断时的基因组情况，并将其与预后和分类相关联。在确定每种病例的基因型和预后时，易位和拷贝数变化（CNA）对基因突变起主要作用。在我们的蛋白酶体抑制剂和IMiD治疗的患者队列中，长期随访的患者中已知和新颖的独立预后标志物，包括具有特定背景预后价值的事件，例如PRDM1基因的缺失。利用每种情况的全面基因组注释，我们使用创新的统计方法来识别潜在的新型骨髓瘤亚组。我们观察到了根据突变总数和CNA的数量/类型分层的患者群，对生存率有明显影响，这表明在诊断时多发性骨髓瘤基因型的扩展可能会改善疾病的分类和预后。 2017年12月6日。doi：10.1038 / leu.2017.344。