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Published in: Archives of Gynecology and Obstetrics 5/2017

01-05-2017 | Gynecologic Oncology

Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study

Authors: Cornelia Meisel, Carolin Eva Sadowski, Daniela Kohlstedt, Katja Keller, Franziska Stäritz, Nannette Grübling, Kerstin Becker, Luisa Mackenroth, Andreas Rump, Evelin Schröck, Norbert Arnold, Pauline Wimberger, Karin Kast

Published in: Archives of Gynecology and Obstetrics | Issue 5/2017

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Abstract

Background

Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants.

Methods

In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA.

Results

Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66).

Conclusion

The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.
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Metadata
Title
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study
Authors
Cornelia Meisel
Carolin Eva Sadowski
Daniela Kohlstedt
Katja Keller
Franziska Stäritz
Nannette Grübling
Kerstin Becker
Luisa Mackenroth
Andreas Rump
Evelin Schröck
Norbert Arnold
Pauline Wimberger
Karin Kast
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 5/2017
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-017-4330-z

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