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The In Vitro Stability of Circulating Tumour DNA

Overview of attention for article published in PLOS ONE, December 2016
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The In Vitro Stability of Circulating Tumour DNA
Published in
PLOS ONE, December 2016
DOI 10.1371/journal.pone.0168153
Pubmed ID

Emanuela Henao Diaz, Jeffrey Yachnin, Henrik Grönberg, Johan Lindberg


DNA from apoptotic cancer cells, present in the circulation, has the potential to facilitate genomic profiling and disease monitoring. However, only low fractions of total cell-free DNA originates from cancer cells, limiting the applicability of circulating tumour DNA (ctDNA). Optimal sample processing is consequently of uttermost importance. Therefore, we evaluated the in vitro stability of ctDNA. Blood was collected in 10 ml EDTA or Streck tubes. Three conditions (EDTA and Streck tubes in room temperature, EDTA tubes at five degrees) and four time points (plasma harvested from blood aliquots of each 10 ml tube in a time series up to 24 h) were investigated. Each condition was evaluated in five metastatic prostate cancer patients. Subsequently, three additional patients were collected enabling investigation of the in vitro stability in EDTA tubes up to 48 h. The in vitro stability of ctDNA was interrogated by low-pass whole genome sequencing which allows for the identification of somatic copy-number alterations (CNAs). In silico simulations demonstrated that non-parametric testing could detect a 1% contamination by white blood cell DNA. Mutational profiling was performed by targeted, in-solution based hybridization capture and subsequent sequencing. The allelic fraction of individual mutations was used as an estimate of the in vitro stability. Somatic CNAs were detected in all patients. Surprisingly, the ctDNA levels at zero hours were not significantly different to 24 or 48 hour in vitro incubation in any investigated condition. Subsequently, mutational profiling corroborated the conclusions from the CNA analysis. The stability of ctDNA simplifies logistics without the requirement of immediate processing or applying fixatives to prevent white blood cell lysis.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 24%
Student > Master 6 18%
Student > Ph. D. Student 5 15%
Student > Bachelor 4 12%
Other 2 6%
Other 4 12%
Unknown 5 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 38%
Medicine and Dentistry 7 21%
Agricultural and Biological Sciences 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Computer Science 1 3%
Other 3 9%
Unknown 6 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 December 2016.
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