An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage.
An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage.
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作者：
循环肿瘤DNA（ctDNA）代表了用于癌症负荷的非侵入性评估的有前景的生物标志物，但是现有方法对于广泛的临床适用性具有不足的灵敏度或患者覆盖率。在这里，我们介绍了通过深度测序（CAPP-Seq）的CAncer个性化分析，这是一种经济且超灵敏的ctDNA定量方法。我们对非小细胞肺癌（NSCLC）实施了CAPP-Seq，其设计涵盖了多种类型的体细胞改变，在>95%的肿瘤中鉴定了突变。我们在100%的II-IV期和50%的I期NSCLC患者中检测到ctDNA，突变等位基因分数的特异性为96%，降至约0.02%。ctDNA水平与肿瘤体积显著相关，区分残留病变和治疗相关的影像学变化，并提供比放射学方法更早的反应评估。最后，我们探索了无活检肿瘤筛查和CAPP-Seq基因分型。我们设想CAPP-Seq可以在临床上常规应用于检测和监测各种恶性肿瘤，从而促进个性化的癌症治疗。
Circulating tumor DNA (ctDNA) represents a promising biomarker for noninvasive assessment of cancer burden, but existing methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non-small cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of stage II–IV and 50% of stage I NSCLC patients, with 96% specificity for mutant allele fractions down to ~0.02%. Levels of ctDNA significantly correlated with tumor volume, distinguished between residual disease and treatment-related imaging changes, and provided earlier response assessment than radiographic approaches. Finally, we explored biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.
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影响因子：
17.1
作者：
Leary RJ;Kinde I;Diehl F;Schmidt K;Clouser C;Duncan C;Antipova A;Lee C;McKernan K;De La Vega FM;Kinzler KW;Vogelstein B;Diaz LA Jr;Velculescu VE
通讯作者：
Velculescu VE
DOI：
10.1073/pnas.0507904102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Diehl, F;Li, M;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
9.3
作者：
Chan, K. C. Allen;Jiang, Peiyong;Lo, Y. M. D.
通讯作者：
Lo, Y. M. D.
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
影响因子：
14.9
作者：
Forbes, Simon A.;Tang, Gurpreet;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew