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HBOC multi-gene panel testing: comparison of two sequencing centers

  • Epidemiology
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Abstract

Multi-gene panels are used to identify genetic causes of hereditary breast and ovarian cancer (HBOC) in large patient cohorts. This study compares the diagnostic workflow in two centers and gives valuable insights into different next-generation sequencing (NGS) strategies. Moreover, we present data from 620 patients sequenced at both centers. Both sequencing centers are part of the German consortium for hereditary breast and ovarian cancer (GC-HBOC). All 620 patients included in this study were selected following standard BRCA1/2 testing guidelines. A set of 10 sequenced genes was analyzed per patient. Twelve samples were exchanged and sequenced at both centers. NGS results were highly concordant in 12 exchanged samples (205/206 variants = 99.51 %). One non-pathogenic variant was missed at center B due to a sequencing gap (no technical coverage). The custom enrichment at center B was optimized during this study; for example, the average number of missing bases was reduced by a factor of four (vers. 1: 1939.41, vers. 4: 506.01 bp). There were no sequencing gaps at center A, but four CCDS exons were not included in the enrichment. Pathogenic mutations were found in 12.10 % (75/620) of all patients: 4.84 % (30/620) in BRCA1, 4.35 % in BRCA2 (27/620), 0.97 % in CHEK2 (6/620), 0.65 % in ATM (4/620), 0.48 % in CDH1 (3/620), 0.32 % in PALB2 (2/620), 0.32 % in NBN (2/620), and 0.16 % in TP53 (1/620). NGS diagnostics for HBOC-related genes is robust, cost effective, and the method of choice for genetic testing in large cohorts. Adding 8 genes to standard BRCA1- and BRCA2-testing increased the mutation detection rate by one-third.

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Acknowledgments

The authors thank all patients and families for their participation in this study. This study was supported by the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstr. 7, 72076, Tübingen, Germany

    Christopher Schroeder, Ulrike Faust, Marc Sturm, Kathrin Grundmann, Florian Harmuth, Kristin Bosse, Martin Kehrer, Tanja Benkert, Mechthilde Heilig, Huu Phuc Nguyen, Olaf Riess & Peter Bauer

  2. Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Karl Hackmann, Barbara Klink, Luisa Mackenroth, Elitza Betcheva-Krajcir, Evelin Schröck & Andreas Rump

  3. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Pauline Wimberger & Karin Kast

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  1. Christopher Schroeder
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Correspondence to Christopher Schroeder.

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Schroeder, C., Faust, U., Sturm, M. et al. HBOC multi-gene panel testing: comparison of two sequencing centers. Breast Cancer Res Treat 152, 129–136 (2015). https://doi.org/10.1007/s10549-015-3429-9

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