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dc.contributor.authorAung, Kyaw Lwin
dc.contributor.authorDonald, E
dc.contributor.authorEllison, G
dc.contributor.authorBujac, S
dc.contributor.authorFletcher, L
dc.contributor.authorCantarini, M
dc.contributor.authorBrady, G
dc.contributor.authorOrr, M
dc.contributor.authorClack, G
dc.contributor.authorRanson, Malcolm R
dc.contributor.authorDive, Caroline
dc.contributor.authorHughes, A
dc.date.accessioned2014-04-17T08:26:06Z
dc.date.available2014-04-17T08:26:06Z
dc.date.issued2014-03-11
dc.identifier.citationAnalytical validation of BRAF mutation testing from circulating free DNA using the amplification refractory mutation testing system. 2014: J Mol Diagnen
dc.identifier.issn1943-7811
dc.identifier.pmid24631158
dc.identifier.doi10.1016/j.jmoldx.2013.12.004
dc.identifier.urihttp://hdl.handle.net/10541/315940
dc.description.abstractBRAF mutation testing from circulating free DNA (cfDNA) using the amplification refractory mutation testing system (ARMS) holds potential as a surrogate for tumor mutation testing. Robust assay validation is needed to establish the optimal clinical matrix for measurement and cfDNA-specific mutation calling criteria. Plasma- and serum-derived cfDNA samples from 221 advanced melanoma patients were analyzed for BRAF c.1799T>A (p.V600E) mutation using ARMS in two stages in a blinded fashion. cfDNA-specific mutation calling criteria were defined in stage 1 and validated in stage 2. cfDNA concentrations in serum and plasma, and the sensitivities and specificities of BRAF mutation detection in these two clinical matrices were compared. Sensitivity of BRAF c.1799T>A (p.V600E) mutation detection in cfDNA was increased by using mutation calling criteria optimized for cfDNA (these criteria were adjusted from those used for archival tumor biopsies) without compromising specificity. Sensitivity of BRAF mutation detection in serum was 44% (95% CI, 35% to 53%) and in plasma 52% (95% CI, 43% to 61%). Specificity was 96% (95% CI, 90% to 99%) in both matrices. Serum contains significantly higher total cfDNA than plasma, whereas the proportion of tumor-derived mutant DNA was significantly higher in plasma. Using mutation calling criteria optimized for cfDNA improves sensitivity of BRAF c.1799T>A (p.V600E) mutation detection. The proportion of tumor-derived cfDNA in plasma was significantly higher than in serum.
dc.languageENG
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of molecular diagnostics : JMDen
dc.titleAnalytical validation of BRAF mutation testing from circulating free DNA using the amplification refractory mutation testing system.en
dc.typeArticleen
dc.contributor.departmentClinical and Experimental Pharmacology Group, CRUK Manchester Institute, Manchesteren
dc.identifier.journalThe Journal of Molecular Diagnosticsen
html.description.abstractBRAF mutation testing from circulating free DNA (cfDNA) using the amplification refractory mutation testing system (ARMS) holds potential as a surrogate for tumor mutation testing. Robust assay validation is needed to establish the optimal clinical matrix for measurement and cfDNA-specific mutation calling criteria. Plasma- and serum-derived cfDNA samples from 221 advanced melanoma patients were analyzed for BRAF c.1799T>A (p.V600E) mutation using ARMS in two stages in a blinded fashion. cfDNA-specific mutation calling criteria were defined in stage 1 and validated in stage 2. cfDNA concentrations in serum and plasma, and the sensitivities and specificities of BRAF mutation detection in these two clinical matrices were compared. Sensitivity of BRAF c.1799T>A (p.V600E) mutation detection in cfDNA was increased by using mutation calling criteria optimized for cfDNA (these criteria were adjusted from those used for archival tumor biopsies) without compromising specificity. Sensitivity of BRAF mutation detection in serum was 44% (95% CI, 35% to 53%) and in plasma 52% (95% CI, 43% to 61%). Specificity was 96% (95% CI, 90% to 99%) in both matrices. Serum contains significantly higher total cfDNA than plasma, whereas the proportion of tumor-derived mutant DNA was significantly higher in plasma. Using mutation calling criteria optimized for cfDNA improves sensitivity of BRAF c.1799T>A (p.V600E) mutation detection. The proportion of tumor-derived cfDNA in plasma was significantly higher than in serum.


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