Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making.
Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making.
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DOI：
10.2147/ott.s81995
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发表时间：
2015
影响因子：
4
通讯作者：
Khemka V
中科院分区：
文献类型：
--
作者：
Weiss GJ;Hoff BR;Whitehead RP;Sangal A;Gingrich SA;Penny RJ;Mallery DW;Morris SM;Thompson EJ;Loesch DM;Khemka V
人们普遍认为，通过下一代测序（NGS）检查癌症的基因组畸变具有重要价值。商业上可用的 NGS 平台如何相互比较，以及所报告的可操作结果的临床效用尚不清楚。在当前研究过程中，Foundation One (F1) 测试生成了约 250× 覆盖范围的体细胞突变、插入和缺失多态性、染色体异常和脱氧核糖核酸 (DNA) 拷贝数变化组合的数据，而 Paradigm Cancer Diagnostic (PCDx) 测试生成了 >5,000× 覆盖范围的相同类型的数据，并提供了信使 RNA (mRNA) 表达水平。我们试图使用这两个平台来比较和评估配对的福尔马林固定石蜡包埋的肿瘤组织。来自晚期实体瘤患者的样本被提交给 F1 和 PCDx 供应商进行 NGS 分析。计算周转时间（TAT）。如果生物标志物与人类治疗反应具有已发表的关联，并且被分配到以下类别：商业药物 (CA)、临床试验药物 (CT) 或两者都没有（以下简称“无”），则认为生物标志物具有临床可操作性。 21 名独特患者肿瘤样本的人口统计数据包括 10 名男性和 11 名女性，中位年龄为 56 岁。由于同一收藏时期的档案组织不足，在一个案例中，我们使用了来自不同收藏的样本。在 20 例病例中，PCDx 报告首次结果的速度比 F1 更快。当两家供应商于同一天收到 PCDx 报告时，PCDx 报告了 15 例中 14 例的首次结果，其中 TAT 中位数比 F1 早 9 天（P<0.0001）。 CA 的分类与 CT 相比，没有一个明显有利于 PCDx（P=0.012）。在当前的分析中，商用 NGS 平台为 47%–67% 的不同癌症类型提供了临床相关的可操作靶点（CA 或 CT）。在分析的样本中，PCDx 在 TAT 方面的表现显着优于 F1，并且具有统计学上显着较高的分类为 CA 的临床相关可操作目标。
It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms. Samples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as “None”). The demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012). In the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%–67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.