文章：

在基因组特征分析方面，配对末端测序优于荧光原位杂交技术用于多发性骨髓瘤研究

Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma

原文发布日期：2019-12-16

DOI: 10.1038/s41408-019-0255-z

类型: Article

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英文摘要：

Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.
 

摘要翻译： 

荧光原位杂交（FISH）是目前检测多发性骨髓瘤（MM）中具有预后意义的复发性基因组异常的金标准检测方法。由于多发性骨髓瘤中的大多数易位涉及具有异质性断点的位置效应，我们假设FISH有可能漏检涉及这些区域的易位。我们通过FISH和全基因组配对末端测序（MPseq）对70例浆细胞疾病患者的骨髓样本进行了评估。在评估每个原发性和继发性异常时，30例（42.9%）显示FISH和MPseq之间存在至少一次不一致。9例通过FISH检测到的异常未被MPseq检测到，包括6例四倍体克隆和3例漏检的拷贝数异常。相比之下，19例通过MPseq检测到的异常未被FISH检测到。其中17例为MYC重排，2例为17p缺失。MPseq识别出36例MYC异常，其中17例（占具有FISH结果的MYC异常组的50.0%）显示FISH假阴性结果。MPseq识别出10例（14.3%）存在IgL重排（近期发现的不良预后标志物），以及10%存在与来那度胺反应或耐药相关基因的异常。总之，在表征重排复杂性和识别继发性异常方面，MPseq优于FISH，显示出比FISH更高的临床价值。

原文链接：

Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma