Myeloma Genome Project Panel is a Comprehensive Targeted Genomics Panel for Molecular Profiling of Patients with Multiple Myeloma.
Myeloma Genome Project Panel is a Comprehensive Targeted Genomics Panel for Molecular Profiling of Patients with Multiple Myeloma.
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骨髓瘤基因组计划小组是一个全面的靶向基因组学小组，用于多发性骨髓瘤患者的分子特征分析。
DOI：
10.1158/1078-0432.ccr-21-3695
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发表时间：
2022-07-01
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我们设计了一个全面的多发性骨髓瘤靶向测序小组，在单一的分析中识别常见的基因组异常，并根据已知的标准进行验证。该小组包括228个突变基因/外显子，6个易位区域和56个拷贝数异常区域（CNA）。为了小组验证，对233例患者样本进行了靶向测序，并使用已知标准（突变）的临床FISH（易位），多重连接探针分析（MLPA; CNAs），全基因组测序（WGS; CNAs，突变，易位）或液滴数字PCR （ddPCR）进一步验证。在43.2%的患者中检测到典型免疫球蛋白重链易位，除1例患者外，与FISH一致。测序和MLPA测定的22个区域的CNAs在103个样本中具有可比性，平台间的一致性R2 = 0.969。测序与ddPCR比较74个突变的变异等位基因频率（VAF），一致性R2 = 0.9849。总之，我们已经开发出一种靶向测序面板，它与FISH和WGS一样健壮或优于后者。这种分子面板具有成本效益、综合性、临床可操作性，可以常规部署，以协助诊断或治疗后的风险分层，以指导治疗的排序。
We designed a comprehensive multiple myeloma targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNA). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical FISH (translocations), multiplex ligation probe analysis (MLPA; CNAs), whole-genome sequencing (WGS; CNAs, mutations, translocations), or droplet digital PCR (ddPCR) of known standards (mutations). Canonical immunoglobulin heavy chain translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for 1 patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2 = 0.969. Variant allele frequency (VAF) for 74 mutations were compared between sequencing and ddPCR with concordance of R2 = 0.9849. In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost-effective, comprehensive, clinically actionable, and can be routinely deployed to assist risk stratification at diagnosis or posttreatment to guide sequencing of therapies.