Universität zu Köln

Heydt, Carina, Becher, Ann-Kathrin, Wagener-Ryczek, Svenja, Ball, Markus, Schultheis, Anne M., Schallenberg, Simon, Ruesseler, Vanessa, Buettner, Reinhard and Merkelbach-Bruse, Sabine (2019). Comparison of in situ and extraction-based methods for the detection of MET amplifications in solid tumors. Comp. Struct. Biotechnol. J.., 17. S. 1339 - 1348. AMSTERDAM: ELSEVIER. ISSN 2001-0370

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Abstract

In EGFR-treatment naive NSCLC patients, high-level MET amplification is detected in approximately 2-3% and is considered as adverse prognostic factor. Currently, clinical trials with two different inhibitors, capmatinib and tepotinib, are under way both defining different inclusion criteria regarding MET amplification from proven amplification only to defining an exact MET copy number. Here, 45 patient samples, including 10 samples without MET amplification, 5 samples showing a low-level MET amplification, 10 samples with an intermediate-level MET amplification, 10 samples having a high-level MET amplification by a MET/CEN7 ratio >= 2.0 and 10 samples showing a high-level MET amplification with GCN >= 6, were evaluated by MET FISH, MET IHC, a ddPCR copy number assay, a NanoString nCounter copy number assay and an amplicon-based parallel sequencing. The MET IHC had the best concordance with MET FISH followed by the NanoString copy number assay, the ddPCR copy number assay and the custom ampliconbased parallel sequencing assays. The concordance was higher in the high-level amplified cohorts than in the low- and intermediate-level amplified cohorts. In summary, currently extraction-based methods cannot replace the MET FISH for the detection of low-level, intermediate-level and high-level MET amplifications, as the number of false negative results is very high. Only for the detection of high-level amplified samples with a gene copy number >= 6 extraction-based methods are a reliable alternative. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Becher, Ann-Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener-Ryczek, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Ball, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultheis, Anne M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schallenberg, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruesseler, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-160103
DOI:	10.1016/j.csbj.2019.09.003
Journal or Publication Title:	Comp. Struct. Biotechnol. J..
Volume:	17
Page Range:	S. 1339 - 1348
Date:	2019
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2001-0370
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL LUNG-CANCER; GENE COPY NUMBER; PHASE-III; MUTATIONS; ACTIVATION; RATIONALE; ERLOTINIB; THERAPY; DESIGN Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16010