A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use in 20 European clinical diagnostic laboratories
Background: Thousands of clinically relevant variations in BRCA1 and BRCA2 have been discovered and this poses a significant challenge with respect to the accurate detection, analysis turn-around time, characterisation and interpretation of these sequence variants. Methods: We evaluated the performa...
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Veröffentlicht in: | British journal of cancer 2017-08, Vol.117 (5), p.710-716 |
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Sprache: | eng |
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Zusammenfassung: | Background:
Thousands of clinically relevant variations in
BRCA1
and
BRCA2
have been discovered and this poses a significant challenge with respect to the accurate detection, analysis turn-around time, characterisation and interpretation of these sequence variants.
Methods:
We evaluated the performance of different
BRCA1/2
gene testing practices in routine diagnostic use in 20 European laboratories, with a focus on next-generation sequencing-based strategies as this is the technical approach implemented by or under adoption by most European clinical laboratories. Participant laboratories, selected on expertise and diagnostic service quality, tested 10 identical DNA samples containing a range of challenging pathogenic variants.
Results:
A small number of errors in the detection of pathogenic and significant variants were identified (2.6% diagnostic error rate). There was a high degree of concordance (>97%) across all laboratories for all variants detected. No systematic technical flaw was identified in the strategies employed across the participating laboratories.
Conclusions:
The discrepancies identified are most likely due to human error or the way the methodology has been implemented locally, for example, next-generation sequencing bioinformatics pipelines, rather than technical limitations of the methods. The choice of
BRCA1/2
testing method will therefore depend on multiple factors including required throughput and turn-around times, access to equipment, expertise and budget. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2017.223 |