Whole genome amplification of cell-free DNA enables detection of circulating tumor DNA mutations from fingerstick capillary blood View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Rekha Gyanchandani, Erik Kvam, Ryan Heller, Erin Finehout, Nicholas Smith, Karthik Kota, John R. Nelson, Weston Griffin, Shannon Puhalla, Adam M. Brufsky, Nancy E. Davidson, Adrian V. Lee

ABSTRACT

The ability to measure mutations in plasma cell-free DNA (cfDNA) has the potential to revolutionize cancer surveillance and treatment by enabling longitudinal monitoring not possible with solid tumor biopsies. However, obtaining sufficient quantities of cfDNA remains a challenge for assay development and clinical translation; consequently, large volumes of venous blood are typically required. Here, we test proof-of-concept for using smaller volumes via fingerstick collection. Matched venous and fingerstick blood were obtained from seven patients with metastatic breast cancer. Fingerstick blood was separated at point-of-care using a novel paper-based concept to isolate plasma centrifuge-free. Patient cfDNA was then analyzed with or without a new method for whole genome amplification via rolling-circle amplification (WG-RCA). We identified somatic mutations by targeted sequencing and compared the concordance of mutation detection from venous and amplified capillary samples by droplet-digital PCR. Patient mutations were detected with 100% concordance after WG-RCA, although in some samples, allele frequencies showed greater variation likely due to differential amplification or primer inaccessibility. These pilot findings provide physiological evidence that circulating tumor DNA is accessible by fingerstick and sustains presence/absence of mutation detection after whole-genome amplification. Further refinement may enable simpler and less-invasive methods for longitudinal or theranostic surveillance of metastatic cancer. More... »

PAGES

17313

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-35470-9

DOI

http://dx.doi.org/10.1038/s41598-018-35470-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110042763

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30470782


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-35470-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-35470-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-35470-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-35470-9'


 

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292 Women’s Cancer Research Center, Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee Womens Research Institute, 15213, Pittsburgh, PA, USA
293 rdf:type schema:Organization
 




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