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

Autor: Jianying Li, Jun Li, Duanming Du, Hao Lin, Fugen Li, Lei Xiong, Zhenghua Zhang, Zhenhua Yang, Nong Yang, Li Yi, Lincan Duan, Xinkai Cao, Li Dongge, Bo Jiang, Hao Qin, Lizhu Lin, Hua Shen, Haiyan Yang, Xiaoqing Cao, Zhidong Liu
Rok vydání: 2018
Předmět:
Adult
Male
Blood tumor mutational burden
UC-seq
0301 basic medicine
Cancer Research
Short ctDNA
DNA Copy Number Variations
Concordance
medicine.disease_cause
Sensitivity and Specificity
lcsh:RC254-282
Circulating Tumor DNA
Capture-base sequencing
03 medical and health sciences
0302 clinical medicine
INDEL Mutation
High complexity
Neoplasms
Biomarkers
Tumor
Genetics
medicine
Humans
Digital polymerase chain reaction
Neoplasm Metastasis
Lung cancer
Volume concentration
Neoplasm Staging
Mutation
Chemistry
Precision medicine
Critical factors
DNA
Neoplasm
Sequence Analysis
DNA
ctDNA
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Molecular biology
Tumor tissue
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Next-generation sequencing
Female
Research Article
Zdroj: BMC Cancer, Vol 18, Iss 1, Pp 1-12 (2018)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-018-4199-7
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12885-018-4199-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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