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


Journal

Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230

Informations de publication

Date de publication:
10 2019
Historique:
received: 16 05 2019
revised: 05 07 2019
accepted: 12 07 2019
pubmed: 16 7 2019
medline: 1 7 2020
entrez: 16 7 2019
Statut: ppublish

Résumé

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. 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 nonprogressive disease. This pronounced biological variation of the circulating DNA should be investigated further to determine whether ctDNA can be used for monitoring cancer activity.

Identifiants

pubmed: 31306545
doi: 10.1002/1878-0261.12546
pmc: PMC6763781
doi:

Substances chimiques

Circulating Tumor DNA 0
DNA, Neoplasm 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2098-2106

Informations de copyright

© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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Auteurs

Johanne A Hojbjerg (JA)

Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.

Anne T Madsen (AT)

Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.

Hjordis H Schmidt (HH)

Department of Oncology, Aarhus University Hospital, Denmark.

Steffen F Sorensen (SF)

Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.

Magnus Stougaard (M)

Department of Pathology, Aarhus University Hospital, Denmark.

Peter Meldgaard (P)

Department of Oncology, Aarhus University Hospital, Denmark.

Boe S Sorensen (BS)

Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.

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Classifications MeSH