An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
Top Cited Papers
Open Access
- 6 April 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 20 (5), 548-554
- https://doi.org/10.1038/nm.3519
Abstract
Aaron Newman and his colleagues introduce a next-generation sequencing–based approach for the cost-effective detection and quantitation of tumor-derived circulating DNA in both early- and advanced-stage tumors and with high levels of sensitivity and specificity. CAPP-Seq (cancer personalized profiling by deep sequencing) can simultaneously detect multiple mutations and mutation types, including rearrangements. Here, utility is demonstrated for non–small-cell lung cancer. Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive assessment of cancer burden, but existing ctDNA detection 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 patients with stage II–IV NSCLC and in 50% of patients with stage I, with 96% specificity for mutant allele fractions down to ∼0.02%. Levels of ctDNA were highly correlated with tumor volume and distinguished between residual disease and treatment-related imaging changes, and measurement of ctDNA levels allowed for earlier response assessment than radiographic approaches. Finally, we evaluated 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.Keywords
This publication has 42 references indexed in Scilit:
- Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencingGenome Medicine, 2013
- Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel SequencingCell, 2012
- Ultrasensitive Measurement of Hotspot Mutations in Tumor DNA in Blood Using Error-Suppressed Multiplexed Deep SequencingCancer Research, 2012
- ROS1 Rearrangements Define a Unique Molecular Class of Lung CancersJournal of Clinical Oncology, 2012
- Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodesProceedings of the National Academy of Sciences, 2012
- Optimizing illumina next-generation sequencing library preparation for extremely at-biased genomesBMC Genomics, 2012
- IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patientsOncotarget, 2011
- Identifying cancer driver genes in tumor genome sequencing studiesBioinformatics, 2010
- Screening for Epidermal Growth Factor Receptor Mutations in Lung CancerNew England Journal of Medicine, 2009
- Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung CancerCell, 2007