文章：

全面检测复发性基因组异常：一种用于多发性骨髓瘤的靶向测序方法

Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma

原文发布日期：2019-12-11

DOI: 10.1038/s41408-019-0264-y

类型: Article

开放获取: 是

英文摘要：

Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era.
 

摘要翻译： 

多发性骨髓瘤的最新基因组研究揭示了超越常规细胞遗传学分类的临床相关分子亚群。要将这些进展应用于临床试验设计和常规患者护理，需要新一代分子诊断工具。本文介绍了一种定制捕获新一代测序（NGS） panel，可在单次检测中识别涉及IGH基因座的易位、臂层和局灶性拷贝数异常，以及多发性骨髓瘤的常见突变基因。我们对154例浆细胞疾病患者进行了测序，并与常规临床检测方法（即荧光原位杂交（FISH）和单核苷酸多态性（SNP）微阵列）的结果进行了头对头比较。我们的定制捕获NGS panel在检测多发性骨髓瘤中IGH易位和相关染色体增益与缺失方面具有高灵敏度（>99%）和特异性（>99%）。此外，该检测还能捕获与不良预后相关的新的基因组标志物，如涉及TP53的双等位事件。总之，我们证明针对多发性骨髓瘤设计的定制捕获NGS panel能够以与FISH和SNP微阵列高度一致的方式检测IGH易位和拷贝数异常，并且重要的是能够捕获多发性骨髓瘤中最相关和最常见的体细胞突变，这使得该方法非常适合现代临床实践的应用。

原文链接：

Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma