Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform.
Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform.
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DOI：
10.18632/oncotarget.3041
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发表时间：
2015-02-10
期刊：
影响因子：
--
通讯作者：
Poultsides GA
中科院分区：
文献类型：
--
作者：
Kidess E;Heirich K;Wiggin M;Vysotskaia V;Visser BC;Marziali A;Wiedenmann B;Norton JA;Lee M;Jeffrey SS;Poultsides GA
循环肿瘤DNA（ctDNA）有望成为实体恶性肿瘤肿瘤监测的非侵入性手段。需要具有高灵敏度和多重突变分析的测定以实现广泛应用。我们开发了一种基于序列特异性同步阻力改变系数（SCODA）技术的新检测方法，该方法富集突变DNA以实现高灵敏度和特异性。将该测定应用于来自非转移性和转移性结直肠癌（CRC）患者的血浆和肿瘤组织，包括因CRC肝转移而进行手术切除的患者。在多项表征实验中，该检测试剂盒证明了该组46种突变中大多数突变的检测限为0.001%（100，000个分子中的1个）。在CRC患者样本（n=38）中，93%的转移性患者与54%的非转移性患者的组织和血浆中检测到的突变一致。对于三名患者，ctDNA鉴定了在肿瘤组织中未检测到的其他突变。在接受肝转移切除术的患者中，ctDNA比癌胚抗原（CEA）值或成像更早预测肿瘤复发。多重SCODA突变富集和检测方法可应用于ctDNA的突变谱分析和定量，并且可能在转移性环境中具有特别的实用性，包括经历转移切除术的患者。
Circulating tumor DNA (ctDNA) holds promise as a non-invasive means for tumor monitoring in solid malignancies. Assays with high sensitivity and multiplexed analysis of mutations are needed to enable broad application. We developed a new assay based on sequence-specific synchronous coefficient of drag alteration (SCODA) technology, which enriches for mutant DNA to achieve high sensitivity and specificity. This assay was applied to plasma and tumor tissue from non-metastatic and metastatic colorectal cancer (CRC) patients, including patients undergoing surgical resection for CRC liver metastases. Across multiple characterization experiments, the assay demonstrated a limit of detection of 0.001% (1 molecule in 100,000) for the majority of the 46 mutations in the panel. In CRC patient samples (n=38), detected mutations were concordant in tissue and plasma for 93% of metastatic patients versus 54% of non-metastatic patients. For three patients, ctDNA identified additional mutations not detected in tumor tissue. In patients undergoing liver metastatectomy, ctDNA anticipated tumor recurrence earlier than carcinoembryonic antigen (CEA) value or imaging. The multiplexed SCODA mutation enrichment and detection method can be applied to mutation profiling and quantitation of ctDNA, and is likely to have particular utility in the metastatic setting, including patients undergoing metastatectomy.
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