Circulating cell-free tumor DNA analysis in pediatric cancers

Daniel Andersson; Henrik Fagman; Martin G Dalin; Anders Ståhlberg

doi:10.1016/j.mam.2019.09.003

Circulating cell-free tumor DNA analysis in pediatric cancers

Mol Aspects Med. 2020 Apr:72:100819. doi: 10.1016/j.mam.2019.09.003. Epub 2019 Sep 25.

Authors

Daniel Andersson¹, Henrik Fagman², Martin G Dalin³, Anders Ståhlberg⁴

Affiliations

¹ Sahlgrenska Cancer Center, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
² Sahlgrenska Cancer Center, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
³ Sahlgrenska Cancer Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Pediatric Oncology, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden.
⁴ Sahlgrenska Cancer Center, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: anders.stahlberg@gu.se.

PMID: 31563277
DOI: 10.1016/j.mam.2019.09.003

Abstract

Analysis of circulating cell-free tumor DNA (ctDNA) has shown promising results within several clinical applications, including cancer detection, mutation profiling, treatment monitoring and early detection of relapse. Here, we discuss the potential and limitations of ctDNA analysis in pediatric cancer detection, therapy decision making and research. Biological properties associated to ctDNA are highlighted and related to technical constraints in downstream analyses. The effects of ctDNA release and clearance dynamics are illustrated and we argue that reporting ctDNA as a fraction of mutated compared to normal wild-type DNA may be problematic from a biological point of view. We have summarized experimental details, data and conclusions from 50 pediatric ctDNA studies. We discuss the genomic landscape of several pediatric entities and how their specific mutation profiles affects ctDNA analysis, often requiring custom-made technical solutions. Finally, we outline future aspects of ctDNA analysis and what is needed to fully implement it into clinical routine in pediatric oncology.

Keywords: Cancer detection; Cancer diagnostics; Circulating cell-free DNA; Circulating cell-free tumor DNA; Liquid biopsy; Pediatric cancer.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biomarkers, Tumor / genetics*
Cell-Free Nucleic Acids / analysis*
Child
Circulating Tumor DNA / analysis*
Circulating Tumor DNA / genetics
Humans
Liquid Biopsy
Neoplasms / genetics*

Substances

Biomarkers, Tumor
Cell-Free Nucleic Acids
Circulating Tumor DNA