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Citation
Tags
HERO ID
3150057
Reference Type
Journal Article
Title
HBOC multi-gene panel testing: comparison of two sequencing centers
Author(s)
Schroeder, C; Faust, U; Sturm, M; Hackmann, K; Grundmann, K; Harmuth, F; Bosse, K; Kehrer, M; Benkert, T; Klink, B; Mackenroth, L; Betcheva-Krajcir, E; Wimberger, P; Kast, K; Heilig, M; Nguyen, HP; Riess, O; Schröck, E; Bauer, P; Rump, A
Year
2015
Is Peer Reviewed?
Yes
Journal
Breast Cancer Research and Treatment
ISSN:
0167-6806
EISSN:
1573-7217
Volume
152
Issue
1
Page Numbers
129-136
Language
English
PMID
26022348
DOI
10.1007/s10549-015-3429-9
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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