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JOURNAL ARTICLE

Intra-individual variation of circulating tumour DNA in lung cancer patients

Johanne A Hojbjerg, Anne T Madsen, Hjordis H Schmidt, Steffen F Sorensen, Magnus Stougaard, Peter Meldgaard, Boe S Sorensen
Molecular Oncology 2019 July 15
31306545
Circulating tumour DNA (ctDNA) has been increasingly incorporated into the treatment of cancer patients. ctDNA is generally accepted as a powerful diagnostic tool, whereas the utility of ctDNA to monitor disease activity needs to be fully validated. Central to this challenge is the question of whether changes in longitudinal ctDNA measurements reflect disease activity or merely biological variation. Thus, the aim of this study was to explore the intra-individual biological variation of ctDNA in lung cancer patients. We identified tumour-specific mutations using next-generation sequencing. Day-to-day and hour-to-hour variations in plasma concentrations of the mutant allele and wild type cell-free DNA (cfDNA) were determined using digital PCR. The levels of the mutant alleles varied by as much as 53% from day-to-day and 27% from hour-to-hour. Cell-free DNA (cfDNA) varied up to 19% from day-to-day and up to 56% from hour-to-hour, as determined using digital PCR. Variations were independent of the concentration. Both mutant allele concentrations and wild type cfDNA concentrations showed considerable intra-individual variation in lung cancer patients with non-progressive disease. This pronounced biological variation of the circulating DNA should be investigated further to determine if ctDNA can be used for monitoring cancer activity. This article is protected by copyright. All rights reserved.

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