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The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues.

The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues.
Author Information (click to view)

Yang N, Li Y, Liu Z, Qin H, Du D, Cao X, Cao X, Li J, Li D, Jiang B, Duan L, Yang H, Zhang Z, Lin H, Li J, Yang Z, Xiong L, Shen H, Lin L, Li F,


Yang N, Li Y, Liu Z, Qin H, Du D, Cao X, Cao X, Li J, Li D, Jiang B, Duan L, Yang H, Zhang Z, Lin H, Li J, Yang Z, Xiong L, Shen H, Lin L, Li F, (click to view)

Yang N, Li Y, Liu Z, Qin H, Du D, Cao X, Cao X, Li J, Li D, Jiang B, Duan L, Yang H, Zhang Z, Lin H, Li J, Yang Z, Xiong L, Shen H, Lin L, Li F,

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BMC cancer 2018 03 2318(1) 319 doi 10.1186/s12885-018-4199-7

Abstract
BACKGROUND
Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues.

METHODS
We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR).

RESULTS
Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA.

CONCLUSIONS
In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.

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