Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

中文翻译：

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使用循环肿瘤DNA直接检测早期癌症。

早期发现和干预可能是降低人类癌症发病率和死亡率的最有效手段。但是，开发无创检测早期肿瘤的方法仍然是一个挑战。我们已经开发出一种称为靶向错误校正测序（TEC-Seq）的方法，该方法可以使用大规模平行测序对循环的无细胞DNA中的序列变化进行超灵敏的直接评估。我们已经使用这种方法来检查58个与癌症相关的基因，涵盖81 kb。对来自44位健康个体的血浆进行的分析确定了16％的无症状个体与克隆性造血相关的基因组变化，但与实体癌相关的驱动基因没有改变。评估200例大肠癌，乳腺癌，肺癌或卵巢癌患者的血浆中存在体细胞突变，I，II期患者分别占59％，59％和68％。对循环中突变的分析显示，这些患者的肿瘤高度一致。在可切除的结直肠癌患者中，术前循环肿瘤DNA的大量增加与疾病复发和总体生存期降低有关。这些分析为非侵入性检测早期肿瘤提供了广泛适用的方法，该方法可用于筛查和治疗癌症患者。术前循环肿瘤DNA的增加与疾病的复发和总体生存率降低有关。这些分析为非侵入性检测早期肿瘤提供了广泛适用的方法，该方法可用于筛查和治疗癌症患者。术前循环肿瘤DNA的增加与疾病的复发和总体生存率降低有关。这些分析为非侵入性检测早期肿瘤提供了广泛适用的方法，该方法可用于筛查和治疗癌症患者。