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dc.contributor.authorO'Leary, B
dc.contributor.authorHrebien, S
dc.contributor.authorBeaney, M
dc.contributor.authorFribbens, C
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorJiang, J
dc.contributor.authorLi, Y
dc.contributor.authorHuang Bartlett, C
dc.contributor.authorAndré, F
dc.contributor.authorLoibl, S
dc.contributor.authorLoi, S
dc.contributor.authorCristofanilli, M
dc.contributor.authorTurner, NC
dc.date.accessioned2019-11-12T15:38:05Z
dc.date.issued2019-11
dc.identifier.citationClinical chemistry, 2019, 65 (11), pp. 1405 - 1413
dc.identifier.issn0009-9147
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3411
dc.identifier.eissn1530-8561
dc.identifier.doi10.1373/clinchem.2019.305805
dc.description.abstractBackground Circulating tumor DNA (ctDNA) assays are increasingly used for clinical decision-making, but it is unknown how well different assays agree. We aimed to assess the agreement in ctDNA mutation calling between BEAMing (beads, emulsion, amplification, and magnetics) and droplet digital PCR (ddPCR), 2 of the most commonly used digital PCR techniques for detecting mutations in ctDNA.Methods Baseline plasma samples from patients with advanced breast cancer enrolled in the phase 3 PALOMA-3 trial were assessed for ESR1 and PIK3CA mutations in ctDNA with both BEAMing and ddPCR. Concordance between the 2 approaches was assessed, with exploratory analyses to estimate the importance of sampling effects.Results Of the 521 patients enrolled, 363 had paired baseline ctDNA analysis. ESR1 mutation detection was 24.2% (88/363) for BEAMing and 25.3% (92/363) for ddPCR, with good agreement between the 2 techniques (κ = 0.9l; 95% CI, 0.85-0.95). PIK3CA mutation detection rates were 26.2% (95/363) for BEAMing and 22.9% (83/363) for ddPCR, with good agreement (κ = 0.87; 95% CI, 0.81-0.93). Discordancy was observed for 3.9% patients with ESR1 mutations and 5.0% with PIK3CA mutations. Assessment of individual mutations suggested higher rates of discordancy for less common mutations ( P = 0.019). The majority of discordant calls occurred at allele frequency <1%, predominantly resulting from stochastic sampling effects.Conclusions This large, clinically relevant comparison showed good agreement between BEAMing and ddPCR, suggesting sufficient reproducibility for clinical use. Much of the observed discordancy may be related to sampling effects, potentially explaining many of the differences in the currently available ctDNA literature.
dc.formatPrint-Electronic
dc.format.extent1405 - 1413
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectEstrogen Receptor alpha
dc.subjectReproducibility of Results
dc.subjectPolymerase Chain Reaction
dc.subjectMutation
dc.subjectFemale
dc.subjectClass I Phosphatidylinositol 3-Kinases
dc.subjectBiomarkers, Tumor
dc.subjectCirculating Tumor DNA
dc.titleComparison of BEAMing and Droplet Digital PCR for Circulating Tumor DNA Analysis.
dc.typeJournal Article
dcterms.dateAccepted2019-08-19
rioxxterms.versionofrecord10.1373/clinchem.2019.305805
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical chemistry
pubs.issue11
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.publication-statusPublished
pubs.volume65
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorBeaney, Matthewen
dc.contributor.icrauthorO'Leary, Benjaminen
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorTurner, Nicholasen


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