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Homologous recombination deficiency as an ovarian cancer biomarker in a real-world cohort: validation of decentralized genomic profiling

The diagnostic evaluation of homologous recombination deficiency (HRD) is central to define targeted therapy strategies for patients with ovarian carcinoma. We evaluated HRD in 514 ovarian carcinoma samples by next-generation sequencing of DNA libraries, including BRCA1/BRCA2 and 26,523 single-nucle...

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Main Authors: Denkert, Carsten (Author) , Romey, Marcel (Author) , Swedlund, Brad (Author) , Hattesohl, Akira (Author) , Teply-Szymanski, Julia (Author) , Kommoss, Stefan (Author) , Kaiser, Kristin (Author) , Staebler, Annette (Author) , du Bois, Andreas (Author) , Grass, Albert (Author) , Knappmeyer, Christiane (Author) , Heitz, Florian (Author) , Solimeno, Cara (Author) , Ebel, Thomas (Author) , Harter, Philipp (Author) , Marmé, Frederik (Author) , Jank, Paul (Author) , Gaiser, Timo (Author) , Neff, Chris (Author) , Wagner, Uwe (Author) , Timms, Kirsten M. (Author) , Rodepeter, Fiona (Author)
Format: Article (Journal)
Language:English
Published: 30 September 2022
In: The journal of molecular diagnostics
Year: 2022, Volume: 24, Issue: 12, Pages: 1254-1263
ISSN:1943-7811
DOI:10.1016/j.jmoldx.2022.09.004
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jmoldx.2022.09.004
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1525157822002665
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Author Notes:Carsten Denkert, Marcel Romey, Brad Swedlund, Akira Hattesohl, Julia Teply-Szymanski, Stefan Kommoss, Kristin Kaiser, Annette Staebler, Andreas du Bois, Albert Grass, Christiane Knappmeyer, Florian Heitz, Cara Solimeno, Thomas Ebel, Philipp Harter, Frederik Marmé, Paul Jank, Timo Gaiser, Chris Neff, Uwe Wagner, Kirsten M. Timms, and Fiona Rodepeter
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Summary:The diagnostic evaluation of homologous recombination deficiency (HRD) is central to define targeted therapy strategies for patients with ovarian carcinoma. We evaluated HRD in 514 ovarian carcinoma samples by next-generation sequencing of DNA libraries, including BRCA1/BRCA2 and 26,523 single-nucleotide polymorphisms using the standardized Myriad HRD assay, with the predefined cut point of ≥42 for a positive genomic instability score (GIS). All samples were measured in the central Myriad laboratory and in an academic molecular pathology laboratory. A positive GIS was detected in 196 (38.1%) of tumors, whereas 318 (61.9%) were GIS negative. Combining GIS and BRCA mutations, a total of 200 (38.9%) of the 514 tumors were HRD positive. A positive GIS was significantly associated with high-grade serous histology (P < 0.000001), grade 3 tumors (P = 0.001), and patient age <60 years (P = 0.0003). The concordance between both laboratories for the GIS status was 96.9% (P < 0.000001), with a sensitivity of 94.6% and a specificity of 98.4%. Concordance for HRD status was 97.1% (499 of 514 tumors). The percentage of HRD-positive tumors in our real-life cohort was similar to the proportion observed in the recently published PAOLA-1 trial, with high concordance between central and local laboratories. Our results support introduction of the standardized HRD assay in academic molecular pathology laboratories, thus broadening access to personalized oncology strategies for patients with ovarian cancer worldwide.
Item Description:Gesehen am 23.05.2023
Physical Description:Online Resource
ISSN:1943-7811
DOI:10.1016/j.jmoldx.2022.09.004

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