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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Nong Yang, Yi Li, Zhidong Liu, Hao Qin, Duanming Du, Xinkai Cao, Xiaoqing Cao, Jun Li, Dongge Li, Bo Jiang, Lincan Duan, Haiyan Yang, Zhenghua Zhang, Hao Lin, Jianying Li, Zhenhua Yang, Lei Xiong, Hua Shen, Lizhu Lin, Fugen Li

Published in: BMC Cancer | Issue 1/2018

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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.
Appendix
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Metadata
Title
The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues
Authors
Nong Yang
Yi Li
Zhidong Liu
Hao Qin
Duanming Du
Xinkai Cao
Xiaoqing Cao
Jun Li
Dongge Li
Bo Jiang
Lincan Duan
Haiyan Yang
Zhenghua Zhang
Hao Lin
Jianying Li
Zhenhua Yang
Lei Xiong
Hua Shen
Lizhu Lin
Fugen Li
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4199-7

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