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QuantiGene Plex – a promising diagnostic tool for cell-of-origin subtyping of diffuse large B cell lymphoma" was successfully entered into The Journal of Molecular Diagnostics
John Simon Hall, Suzanne Usher, Richard John Byers, Rebekah Clare Higgins, Danish Memon, John Anthony Radford and Kim M Linton
The Journal of Molecular Diagnostics. 2015;.
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Abstract
Background: In the era of cell-of-origin targeted therapeutics, personalized management of DLBCL requires co-development of a companion diagnostic assay for ABC/GCB subtyping. Current classification methods are costly/complex (microarray expression profiling) or lack reproducibility and diagnostic precision (immunophenotyping). We investigated the potential of QuantiGene Plex (QGP), a branched DNA signal amplification assay, as a low-cost option with high detection sensitivity from formalin-fixed paraffin embedded (FFPE) tissue. Methods: We performed in silico analysis of public DLBCL datasets to develop/validate a naïve Bayes classifier. The 21-gene classifier was migrated to QGP and qPCR assays for re-classification of 40 DLBCL FFPE tumors of known subtype (20 ABC, 20 GCB by gene expression profiling of paired fresh-frozen tissues). Data were compared for recapitulation of microarray data and classification accuracy. Results: The 21-gene Bayesian classifier achieved mean AUC values >0.9 on independent validation. QGP was performed on 38/40 samples for 21/21 targets. qPCR was performed on 40/40 samples for 19/21 targets. QGP showed a higher correlation with microarray data (mean R2 0.66±0.05 vs 0.34±0.07, p<0.0001) and classification accuracy (92.1% vs 78.9%). The proportion of validated targets was also higher for QGP (85.7% vs 47.4%). The QGP protocol was rapid and simple to perform, at a cost similar to qPCR. Conclusions: These promising preliminary results strongly support ongoing work to develop a QGP DLBCL companion diagnostic assay.
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- MRC - RESMRC