Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan, Republic of China.
Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China.
J Cancer Res Clin Oncol. 2018 Nov;144(11):2167-2175. doi: 10.1007/s00432-018-2747-9. Epub 2018 Sep 10.
Analysis of circulating tumor DNA (ctDNA) offers an unbiased and noninvasive way to assess the genetic profiles of tumors. This study aimed to analyze mutations in ctDNA and their correlation with tissue mutations in patients with a variety of cancers.
We included 21 cancer patients treated with surgical resection for whom we collected paired tissue and plasma samples. Next-generation sequencing (NGS) of all exons was performed in a targeted human comprehensive cancer panel consisting of 275 genes.
Six patients had at least one mutation that was concordant between tissue and ctDNA sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing, 20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing identified driver mutations in 66.67% and 47.62% of the tested samples, respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and 33.33% of patients, respectively. When somatic alterations identified by each test were combined, the total proportion of patients with actionable mutations increased to 71.43%. Moreover, variants of unknown significance that were judged likely pathogenic had a higher percentage in ctDNA exclusively. Across six representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity and specificity of detection using mutations in tissue sample as a reference were 25 and 96.74%, respectively.
This study indicates that tissue NGS and ctDNA NGS are complementary rather than exclusive approaches; these data support the idea that ctDNA is a promising tool to interrogate cancer genetics.
分析循环肿瘤 DNA（ctDNA）提供了一种非侵入性、无偏倚的方法来评估肿瘤的遗传特征。本研究旨在分析不同癌症患者 ctDNA 中的突变及其与组织突变的相关性。
我们纳入了 21 名接受手术切除治疗的癌症患者，采集了配对的组织和血浆样本。使用靶向人类综合癌症panel（包含 275 个基因）对所有外显子进行了下一代测序（NGS）。
6 名患者的组织和 ctDNA 测序中至少有一个突变是一致的。在组织和血液测序中检测到的所有突变（n=35）中，有 20%（n=7）在基因水平上是一致的。组织和 ctDNA 测序分别在 66.67%和 47.62%的检测样本中鉴定出驱动突变。组织和 ctDNA NGS 分别在 57.14%和 33.33%的患者中检测到可操作的改变。当每个测试确定的体细胞改变组合在一起时，具有可操作突变的患者总比例增加到 71.43%。此外，仅在 ctDNA 中鉴定出更多具有未知意义的变异，这些变异被判断为可能具有致病性。在六个代表性基因（PIK3CA、CTNNB1、AKT1、KRAS、TP53 和 MET）中，以组织样本中的突变作为参考，检测的敏感性和特异性分别为 25%和 96.74%。
本研究表明组织 NGS 和 ctDNA NGS 是互补而非排他的方法；这些数据支持了 ctDNA 是一种有前途的癌症遗传学检测工具的观点。
