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01.07.2015 | Epidemiology

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

verfasst von: 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

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2015

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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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Titel: HBOC multi-gene panel testing: comparison of two sequencing centers
verfasst von: 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
Publikationsdatum: 01.07.2015
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2015
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3429-9

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25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

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

Abstract

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Abstract

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