Next-generation Sequencing (NGS) of cancer tissues is increasingly being carried out to identify somatic genomic alterations that may guide physicians to make therapeutic decisions. However, a single tissue biopsy may not reflect complete genomic architecture due to the heterogeneous nature of tumors. Circulating tumor DNA (ctDNA) analysis is a robust noninvasive method to detect and monitor genomic alterations in blood in real time. We analyzed 28 matched tissue NGS and ctDNA from gastrointestinal and lung cancers for concordance of somatic genomic alterations, driver, and actionable alterations. Six patients (21%) had at least one concordant mutation between tissue and ctDNA sequencing. At the gene level, among all the mutations (n = 104) detected by tissue and blood sequencing, 7.7% (n = 8) of mutations were concordant. Tissue and ctDNA sequencing identified driver mutations in 60% and 64% of the tested samples, respectively. We found high discordance between tissue and ctDNA testing, especially with respect to the driver and actionable alterations. Both tissue and ctDNA NGS detected actionable alterations in 25% of patients. When somatic alterations identified by each test were combined, the total number of patients with actionable mutations increased to 32%. Our data show significant discordance between tissue NGS and ctDNA analysis. These results suggest tissue NGS and ctDNA NGS are complementary approaches rather than exclusive of each other. When performed in isolation, tissue and ctDNA NGS can each potentially miss driver and targetable alterations, suggesting that both approaches should be incorporated to enhance mutation detection rates. Larger prospective studies are needed to better clarify this emerging precision oncology landscape. Mol Cancer Ther; 17(5); 1123–32. ©2018 AACR.

中文翻译：

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使用下一代测序的组织基因组学和 ctDNA 之间体细胞基因组改变的相关性：肺癌和胃肠癌的分析。

癌症组织的下一代测序 (NGS) 越来越多地用于识别体细胞基因组改变，这些改变可以指导医生做出治疗决定。然而，由于肿瘤的异质性，单个组织活检可能无法反映完整的基因组结构。循环肿瘤 DNA (ctDNA) 分析是一种强大的非侵入性方法，可实时检测和监测血液中的基因组变化。我们分析了来自胃肠道癌和肺癌的 28 个匹配的组织 NGS 和 ctDNA，以了解体细胞基因组改变、驱动因素和可操作改变的一致性。6 名患者 (21%) 在组织和 ctDNA 测序之间至少有一个一致突变。在基因水平上，在组织和血液测序检测到的所有突变（n = 104）中，7.7%（n = 8）的突变是一致的。组织和 ctDNA 测序分别在 60% 和 64% 的测试样本中确定了驱动突变。我们发现组织和 ctDNA 测试之间存在高度不一致，特别是在驱动程序和可操作的改变方面。组织和 ctDNA NGS 在 25% 的患者中都检测到了可操作的改变。当结合每个测试确定的体细胞改变时，具有可操作突变的患者总数增加到 32%。我们的数据显示组织 NGS 和 ctDNA 分析之间存在显着差异。这些结果表明组织 NGS 和 ctDNA NGS 是互补的方法，而不是相互排斥。当单独进行时，组织和 ctDNA NGS 都可能会错过驱动程序和可靶向的改变，这表明应该结合这两种方法来提高突变检测率。需要更大规模的前瞻性研究来更好地阐明这一新兴的精准肿瘤学领域。摩尔癌症治疗; 17(5); 1123-32。©2018 AACR。