Comparison of variant allele frequency and number of mutant molecules as units of measurement for circulating tumor DNA

Molecular Oncology

卷:15

Evert deJonge¹  Ron H. N. vanSchaik¹  Marzia Del Re¹  Kazem Nasserinejad²  John W. M. Martens³  Stefan Sleijfer³  Manouk K. Bos³  Maurice P. H. M. Jansen³  Lindsay Angus³  Peggy N. Atmodimedjo⁴  Winand N. M. Dinjens⁴  Hendrikus J. Dubbink⁴  Christi M.J. Steendam⁵ 

[1] Department of Clinical Chemistry Erasmus University Medical Center Rotterdam The Netherlands;

[2] Department of Hematology HOVON Data Center Erasmus MC Cancer Institute, University Medical Center Rotterdam The Netherlands;

[3] Department of Medical Oncology Erasmus MC Cancer Institute, University Medical Center Rotterdam The Netherlands;

[4] Department of Pathology Erasmus MC Cancer Institute, University Medical Center Rotterdam The Netherlands;

[5] Department of Pulmonary Medicine Erasmus MC Cancer Institute, University Medical Center Rotterdam The Netherlands;

关键词: cancer;    circulating tumor DNA;    digital droplet PCR;    liquid biopsy;    next‐generation sequencing;    unit of measurement;   

DOI  :  10.1002/1878-0261.12827

来源: DOAJ

【 摘 要 】

Quantification of tumor‐specific variants (TSVs) in cell‐free DNA is rapidly evolving as a prognostic and predictive tool in patients with cancer. Currently, both variant allele frequency (VAF) and number of mutant molecules per mL plasma are used as units of measurement to report those TSVs. However, it is unknown to what extent both units of measurement agree and what are the factors underlying an existing disagreement. To study the agreement between VAF and mutant molecules in current clinical studies, we analyzed 1116 TSVs from 338 patients identified with next‐generation sequencing (NGS) or digital droplet PCR (ddPCR). On different study cohorts, a Deming regression analysis was performed and its 95% prediction interval was used as surrogate for the limits of agreement between VAF and number of mutant molecules per mL and to identify outliers. VAF and number of mutant molecules per mL plasma yielded greater agreement when using ddPCR than NGS. In case of discordance between VAF and number of mutant molecules per mL, insufficient molecular coverage in NGS and high cell‐free DNA concentration were the main responsible factors. We propose several optimization steps needed to bring monitoring of TSVs in cell‐free DNA to its full potential.

【 授权许可】

Unknown