Strategies for improving detection of circulating tumor DNA using next generation sequencing

Tébar-Martínez Roberto; Martín-Arana Jorge; Gimeno-Valiente Francisco; Tarazona Noelia; Rentero-Garrido Pilar; Cervantes Andrés

doi:10.1016/j.ctrv.2023.102595

Strategies for improving detection of circulating tumor DNA using next generation sequencing

Cancer Treat Rev. 2023 Sep:119:102595. doi: 10.1016/j.ctrv.2023.102595. Epub 2023 Jun 25.

Authors

Tébar-Martínez Roberto¹, Martín-Arana Jorge², Gimeno-Valiente Francisco³, Tarazona Noelia⁴, Rentero-Garrido Pilar⁵, Cervantes Andrés⁶

Affiliations

¹ Department of Medical Oncology, INCLIVA Health Research Institute, University of Valencia, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Precision Medicine Unit, INCLIVA Health Research Institute, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain. Electronic address: robertotebarmartinez@gmail.com.
² Department of Medical Oncology, INCLIVA Health Research Institute, University of Valencia, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Bioinformatics Unit, INCLIVA Health Research Institute, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain. Electronic address: jmartin@incliva.es.
³ Cancer Evolution and Genome Instability Laboratory, University College of London Cancer Institute, 72 Huntley St, WC1E 6DD London, United Kingdom. Electronic address: fgimenovaliente@gmail.com.
⁴ Department of Medical Oncology, INCLIVA Health Research Institute, University of Valencia, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Health Institute Carlos III, CIBERONC, C/ Sinesio Delgado, 4, 28029 Madrid, Spain. Electronic address: noetalla@incliva.es.
⁵ Precision Medicine Unit, INCLIVA Health Research Institute, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain. Electronic address: prentero@incliva.es.
⁶ Department of Medical Oncology, INCLIVA Health Research Institute, University of Valencia, C. de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Health Institute Carlos III, CIBERONC, C/ Sinesio Delgado, 4, 28029 Madrid, Spain. Electronic address: andres.cervantes@uv.es.

PMID: 37390697
DOI: 10.1016/j.ctrv.2023.102595

Abstract

Cancer has become a global health issue and liquid biopsy has emerged as a non-invasive tool for various applications. In cancer, circulating tumor DNA (ctDNA) can be detected from cell-free DNA (cfDNA) obtained from plasma and has potential for early diagnosis, treatment, resistance, minimal residual disease detection, and tumoral heterogeneity identification. However, the low frequency of ctDNA requires techniques for accurate analysis. Multitarget assay such as Next Generation Sequencing (NGS) need improvement to achieve limits of detection that can identify the low frequency variants present in the cfDNA. In this review, we provide a general overview of the use of cfDNA and ctDNA in cancer, and discuss techniques developed to optimize NGS as a tool for ctDNA detection. We also summarize the results obtained using NGS strategies in both investigational and clinical contexts.

Keywords: Liquid biopsy; Molecular Barcoding; UMI; ctDNA.

Publication types

Review

MeSH terms

Biomarkers, Tumor / genetics
Cell-Free Nucleic Acids*
Circulating Tumor DNA*
High-Throughput Nucleotide Sequencing / methods
Humans
Mutation
Neoplasms* / diagnosis
Neoplasms* / genetics

Substances

Circulating Tumor DNA
Cell-Free Nucleic Acids
Biomarkers, Tumor