文章：

一种DNA靶向富集方法用于检测多发性骨髓瘤中的突变、拷贝数变化和免疫球蛋白易位

A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma

原文发布日期：2016-09-02

DOI: 10.1038/bcj.2016.72

类型: Original Article

开放获取: 是

英文摘要：

Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines. We identified 548 likely oncogenic mutations in 182 genes. By integrating published data sets of NGS in MM, we retrieved a list of genes with significant relevance to myeloma and found that the mutational spectrum of primary samples and MM cell lines is partially overlapping. Gains and losses of chromosomes, chromosomal segments and gene loci were identified with accuracy comparable to conventional arrays, allowing identification of lesions with known prognostic significance. Furthermore, we identified IGH translocations with high positive and negative predictive value. Our approach could allow the identification of novel biomarkers with clinical relevance in myeloma.

摘要翻译： 

在多发性骨髓瘤（MM）的常规诊断过程中，基因组损伤并未被纳入研究。细胞遗传学检查用于评估预后，但对治疗决策的影响有限。近期研究发现多个反复突变的基因，但其临床价值仍有待明确。因此，需要建立临床级别的骨髓瘤样本基因组图谱研究策略，以整合新型与传统预后标志物。我们开发了一种靶向富集策略结合二代测序技术（NGS），可高效同步分析多发性骨髓瘤的基因突变、拷贝数变异和免疫球蛋白重链（IGH）易位，并在细胞系组中进行了验证。共在182个基因中识别出548个可能致癌的突变。通过整合已发表的多发性骨髓瘤NGS数据集，我们筛选出与骨髓瘤显著相关的基因列表，发现原代样本与骨髓瘤细胞系的突变谱存在部分重叠。染色体、染色体片段及基因位点的增加与缺失检测精度与传统芯片技术相当，能够识别具有已知预后意义的损伤。此外，我们鉴定IGH易位的阳性与阴性预测值均较高。本方法有望识别出具有骨髓瘤临床相关性的新型生物标志物。

原文链接：

A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma