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Open Access 01-06-2019 | Fluorescence in Situ Hybridization | Original Article

Recommendations for the clinical interpretation and reporting of copy number gains using gene panel NGS analysis in routine diagnostics

Authors: Astrid Eijkelenboom, Bastiaan B. J. Tops, Anke van den Berg, Adrianus J. C. van den Brule, Winand N. M. Dinjens, Hendrikus J. Dubbink, Arja ter Elst, Willemina R. R. Geurts-Giele, Patricia J. T. A. Groenen, Floris H. Groenendijk, Daniëlle A. M. Heideman, Manon M. H. Huibers, Cornelis J. J. Huijsmans, Judith W. M. Jeuken, Léon C. van Kempen, Esther Korpershoek, Leonie I. Kroeze, Wendy W. J. de Leng, Carel J. M. van Noesel, Ernst-Jan M. Speel, Maartje J. Vogel, Tom van Wezel, Petra M. Nederlof, Ed Schuuring, Marjolijn J. L. Ligtenberg

Published in: Virchows Archiv | Issue 6/2019

Abstract

Next-generation sequencing (NGS) panel analysis on DNA from formalin-fixed paraffin-embedded (FFPE) tissue is increasingly used to also identify actionable copy number gains (gene amplifications) in addition to sequence variants. While guidelines for the reporting of sequence variants are available, guidance with respect to reporting copy number gains from gene-panel NGS data is limited. Here, we report on Dutch consensus recommendations obtained in the context of the national Predictive Analysis for THerapy (PATH) project, which aims to optimize and harmonize routine diagnostics in molecular pathology. We briefly discuss two common approaches to detect gene copy number gains from NGS data, i.e., the relative coverage and B-allele frequencies. In addition, we provide recommendations for reporting gene copy gains for clinical purposes. In addition to general QC metrics associated with NGS in routine diagnostics, it is recommended to include clinically relevant quantitative parameters of copy number gains in the clinical report, such as (i) relative coverage and estimated copy numbers in neoplastic cells, (ii) statistical scores to show significance (e.g., z-scores), and (iii) the sensitivity of the assay and restrictions of NGS-based detection of copy number gains. Collectively, this information can guide clinical and analytical decisions such as the reliable detection of high-level gene amplifications and the requirement for additional in situ assays in case of borderline results or limited sensitivity.

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Title: Recommendations for the clinical interpretation and reporting of copy number gains using gene panel NGS analysis in routine diagnostics
Authors: Astrid Eijkelenboom
Bastiaan B. J. Tops
Anke van den Berg
Adrianus J. C. van den Brule
Winand N. M. Dinjens
Hendrikus J. Dubbink
Arja ter Elst
Willemina R. R. Geurts-Giele
Patricia J. T. A. Groenen
Floris H. Groenendijk
Daniëlle A. M. Heideman
Manon M. H. Huibers
Cornelis J. J. Huijsmans
Judith W. M. Jeuken
Léon C. van Kempen
Esther Korpershoek
Leonie I. Kroeze
Wendy W. J. de Leng
Carel J. M. van Noesel
Ernst-Jan M. Speel
Maartje J. Vogel
Tom van Wezel
Petra M. Nederlof
Ed Schuuring
Marjolijn J. L. Ligtenberg
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keywords: Fluorescence in Situ Hybridization
Targeted Therapy
Pathology
Published in: Virchows Archiv / Issue 6/2019
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02555-3

ACC 2024 Congress

Springer Medicine

Recommendations for the clinical interpretation and reporting of copy number gains using gene panel NGS analysis in routine diagnostics

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

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