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

Christopher Schroeder*, Ulrike Faust, Marc Sturm, Karl Hackmann, Kathrin Grundmann, Florian Harmuth, Kristin Bosse, Martin Kehrer, Tanja Benkert, Barbara Klink, Luisa Mackenroth, Elitza Betcheva-Krajcir, Pauline Wimberger, Karin Kast, Mechthilde Heilig, Huu Phuc Nguyen, Olaf Riess, Evelin Schröck, Peter Bauer, Andreas Rump

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalBreast Cancer Research and Treatment
Issue number1
Publication statusPublished - 17 Jul 2015
Externally publishedYes


  • Amplicon
  • Benchmark test
  • Cancer susceptibility
  • Capture
  • Next-generation sequencing


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