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dc.contributor.authorGevensleben, H
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorGraeser, MK
dc.contributor.authorSchiavon, G
dc.contributor.authorOsin, P
dc.contributor.authorParton, M
dc.contributor.authorSmith, IE
dc.contributor.authorAshworth, A
dc.contributor.authorTurner, NC
dc.date.accessioned2018-06-14T13:38:52Z
dc.date.issued2013-06
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2013, 19 (12), pp. 3276 - 3284
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1885
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-12-3768
dc.description.abstractPurpose Digital PCR is a highly accurate method of determining DNA concentration. We adapted digital PCR to determine the presence of oncogenic amplification through noninvasive analysis of circulating free plasma DNA and exemplify this approach by developing a plasma DNA digital PCR assay for HER2 copy number.Experimental design The reference gene for copy number assessment was assessed experimentally and bioinformatically. Chromosome 17 pericentromeric probes were shown to be suboptimal, and EFTUD2 at chromosome position 17q21.31 was selected for analysis. Digital PCR assay parameters were determined on plasma samples from a development cohort of 65 patients and assessed in an independent validation cohort of plasma samples from 58 patients with metastatic breast cancer. The sequential probability ratio test was used to assign the plasma DNA digital PCR test as being HER2-positive or -negative in the validation cohort.Results In the development cohort, the HER2:EFTUD2 plasma DNA copy number ratio had a receiver operator area under the curve (AUC) = 0.92 [95% confidence interval (CI), 0.86-0.99, P = 0.0003]. In the independent validation cohort, 64% (7 of 11) of patients with HER2-amplified cancers were classified as plasma digital PCR HER2-positive and 94% (44 of 47) of patients with HER2-nonamplified cancers were classified as digital PCR HER2-negative, with a positive and negative predictive value of 70% and 92%, respectively.Conclusion Analysis of plasma DNA with digital PCR has the potential to screen for the acquisition of HER2 amplification in metastatic breast cancer. This approach could potentially be adapted to the analysis of any locus amplified in cancer.
dc.formatPrint-Electronic
dc.format.extent3276 - 3284
dc.languageeng
dc.language.isoeng
dc.subjectChromosomes, Human, Pair 17
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectNeoplasm Metastasis
dc.subjectReceptor, erbB-2
dc.subjectRibonucleoprotein, U5 Small Nuclear
dc.subjectPeptide Elongation Factors
dc.subjectDNA, Neoplasm
dc.subjectPolymerase Chain Reaction
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectDNA Copy Number Variations
dc.titleNoninvasive detection of HER2 amplification with plasma DNA digital PCR.
dc.typeJournal Article
rioxxterms.versionofrecord10.1158/1078-0432.ccr-12-3768
rioxxterms.licenseref.startdate2013-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue12
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/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume19
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEndocrinologyen_US
icr.researchteamGene Functionen_US
dc.contributor.icrauthorSmith, Ianen
dc.contributor.icrauthorGevensleben, Heidrunen
dc.contributor.icrauthorAshworth, Alanen
dc.contributor.icrauthorTurner, Nicholasen
dc.contributor.icrauthorGarcia-Murillas, Isaacen


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