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Epitranscriptomics & Cancer Adaptation : A.David

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Last modified by pcoopman
Group name EquipePC
Item Type Journal Article
Title A multicenter blinded study evaluating EGFR and KRAS mutation testing methods in the clinical non-small cell lung cancer setting--IFCT/ERMETIC2 Project Part 1: Comparison of testing methods in 20 French molecular genetic National Cancer Institute platforms
Creator Beau-Faller et al.
Author M. Beau-Faller
Author H. Blons
Author C. Domerg
Author D. Gajda
Author N. Richard
Author F. Escande
Author J. Solassol
Author M. G. Denis
Author A. Cayre
Author I. Nanni-Metellus
Author S. Olschwang
Author S. Lizard
Author F. Piard
Author J. L. Pretet
Author F. de Fraipont
Author I. Bieche
Author P. de Cremoux
Author I. Rouquette
Author P. P. Bringuier
Author J. Mosser
Author M. Legrain
Author A. C. Voegeli
Author P. Saulnier
Author F. Morin
Author J. P. Pignon
Author G. Zalcman
Author J. Cadranel
Abstract Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have limited use as first-line treatment for mutated EGFR metastatic non-small cell lung cancer. The French National Cancer Institute has installed molecular genetics platforms implementing EGFR and KRAS testing. However, there is considerable uncertainty as to which detection methods should be applied for routine diagnosis. This study aimed to compare the EGFR and KRAS genotyping methods developed by the IFCT/ERMETIC2 network platforms in two blind panels: 25 samples of serial dilutions of cell line DNA (20 centers) and 74 FFPE lung tumor samples (10 centers). The best threshold of mutation detection on cell lines was obtained using allele-specific amplification-based technologies. Nonamplifiable tissue samples were significantly less common when using alternative testing versus direct sequencing [15%; 95% confidence interval (CI), 14%-16% versus 40%; 95% CI, 39%-42%; P < 0.001]. Mutated cases increased from 42% (95% CI, 31%-54%) to 53% (95% CI, 41%-64%), with three supplementary EGFR mutations (p.G179A at exon 18 and p.L858R and p.L861Q at exon 21) and five supplementary KRAS mutations, when using alternative testing instead of direct sequencing. False-positive results were observed when using a PCR-based sizing assay, high-resolution melting, or pyrosequencing. Concordance analysis returned good kappa test scores for EGFR exon 19 and KRAS analysis when comparing sequencing with alternative methods and revealed no difference between alternative techniques themselves.
Publication J Mol Diagn
Volume 16
Pages 45-55
Date Jan 2014
Journal Abbr The Journal of molecular diagnostics : JMD
DOI 10.1016/j.jmoldx.2013.07.009
ISSN 1943-7811 (Electronic) 1525-1578 (Linking)
Tags Adenocarcinoma/*diagnosis/drug therapy/genetics, Antineoplastic Agents/therapeutic use, Base Sequence, Carcinoma, Non-Small-Cell Lung/*diagnosis/drug therapy/genetics, Cell Line, Tumor, clin, clinic, False Positive Reactions, Genotype, High-Throughput Nucleotide Sequencing/methods, Humans, Lung Neoplasms/*diagnosis/drug therapy/genetics, Molecular Diagnostic Techniques/methods, Nucleic Acid Amplification Techniques, Protein Kinase Inhibitors/therapeutic use, Proto-Oncogene Proteins/*genetics, Quinazolines/therapeutic use, ras Proteins/*genetics, Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics, Sequence Analysis, DNA/*methods
Date Added 2018/11/14 - 12:07:50
Date Modified 2019/05/16 - 16:01:56
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