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

Eijkelenboom, A., Tops, B. B. J., van den Berg, A., van den Brule, A. J. C., Dinjens, W. N. M., Dubbink, H. J., ter Elst, A., Geurts-Giele, W. R. R., Groenen, P. J. T. A., Groenendijk, F. H., Heideman, D. A. M., Huibers, M. M. H., Huijsmans, C. J. J., Jeuken, J. W. M., van Kempen, L. C., Korpershoek, E., Kroeze, L. I., de Leng, W. W. J., van Noesel, C. J. M., Speel, E-J. M., Vogel, M. J., van Wezel, T., Nederlof, P. M., Schuuring, E. & Ligtenberg, M. J. L., Jun-2019, In : Virchows Archiv : an International Journal of Pathology. 474, 6, p. 673-680 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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
  • Danielle A. M. Heideman
  • Manon M. H. Huibers
  • Cornelis J. J. Huijsmans
  • Judith W. M. Jeuken
  • Leon 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

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.

Original languageEnglish
Pages (from-to)673-680
Number of pages8
JournalVirchows Archiv : an International Journal of Pathology
Volume474
Issue number6
Publication statusPublished - Jun-2019

    Keywords

  • Copy number gain, Amplification, NGS, Targeted therapy, Routine diagnostics, Molecular pathology, MOLECULAR-PATHOLOGY, MUTATIONS, MET, ASSOCIATION, VARIANTS, ONCOLOGY

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