High Concordance of Different Assays in the Determination of Homologous Recombination Deficiency–Associated Genomic Instability in Ovarian Cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • German HRD assay Harmonization Consortium - (Author)
  • Nicole Pfarr - , Technical University of Munich (Author)
  • Karin von Schwarzenberg - , Technical University of Munich (Author)
  • Dario Zocholl - , Charité – Universitätsmedizin Berlin (Author)
  • Sabine Merkelbach-Bruse - , University of Cologne (Author)
  • Janna Siemanowski - , University of Cologne (Author)
  • Eva Maria Mayr - , Technical University of Munich (Author)
  • Sylvia Herold - , University Hospital Carl Gustav Carus Dresden, Institute of Pathology (Author)
  • Karsten Kleo - , Berlin Institute of Health at Charité (Author)
  • Lukas C. Heukamp - , Institute for Hematopathology Hamburg GmbH, North-Eastern German Society of Gynecological Oncology (NOGGO) (Author)
  • Eva Maria Willing - , Institute for Hematopathology Hamburg GmbH, North-Eastern German Society of Gynecological Oncology (NOGGO) (Author)
  • Michael Menzel - , Heidelberg University  (Author)
  • Ulrich Lehmann - , Hannover Medical School (MHH) (Author)
  • Stephan Bartels - , Hannover Medical School (MHH) (Author)
  • Shounak Chakraborty - , Technical University of Munich (Author)
  • Gustavo Baretton - , Institute of Pathology, University Hospital Carl Gustav Carus Dresden (Author)
  • Melanie C. Demes - , University Hospital Frankfurt (Author)
  • Claudia Döring - , University Hospital Frankfurt (Author)
  • Daniel Kazdal - , Heidelberg University  (Author)
  • Jan Budczies - , Heidelberg University  (Author)
  • Roland Rad - , Technical University of Munich (Author)
  • Peter Wild - , University Hospital Frankfurt (Author)
  • Yann Christinat - , Geneva University Hospitals (Author)
  • Thomas McKee - , Geneva University Hospitals (Author)
  • Peter Schirmacher - , Heidelberg University  (Author)
  • David Horst - , Berlin Institute of Health at Charité (Author)
  • Reinhard Büttner - , University of Cologne (Author)
  • Albrecht Stenzinger - , Heidelberg University  (Author)
  • Jalid Sehouli - , North-Eastern German Society of Gynecological Oncology (NOGGO), Charité – Universitätsmedizin Berlin (Author)
  • Claudia Vollbrecht - , Berlin Institute of Health at Charité (Author)
  • Michael Hummel - , Berlin Institute of Health at Charité (Author)
  • Elena I. Braicu - , North-Eastern German Society of Gynecological Oncology (NOGGO), Charité – Universitätsmedizin Berlin (Author)
  • Wilko Weichert - , Technical University of Munich (Author)

Abstract

PURPOSE Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used for the detection of HRD in clinical studies is the Myriad myChoice assay. However, other assays can also be used to assess biomarkers, which are indicative of HRD, genomic instability (GI), and BRCA1/2 mutation status. Many of these assays have high potential to be broadly applied in clinical routine diagnostics in a time-effective decentralized manner. Here, we compare the performance of a multitude of alternative assays in comparison with Myriad myChoice in high-grade serous ovarian cancer (HGSOC). METHODS DNA from HGSOC samples was extracted from formalin-fixed paraffin-embedded tissue blocks of cases previously run with the Myriad myChoice assay, and GI was measured by multiple molecular assays (CytoSNP, AmoyDx, Illumina TSO500 HRD, OncoScan, NOGGO GISv1, QIAseq HRD Panel and whole genome sequencing), applying different bioinformatics algorithms. RESULTS Application of different assays to assess GI, including Myriad myChoice, revealed high concordance of the generated scores ranging from very substantial to nearly perfect fit, depending on the assay and bioinformatics pipelines applied. Interlaboratory comparison of assays also showed high concordance of GI scores. CONCLUSION Assays for GI assessment not only show a high concordance with each other but also in correlation with Myriad myChoice. Thus, almost all of the assays included here can be used effectively to assess HRD-associated GI in the clinical setting. This is important as PARPi treatment on the basis of these tests is compliant with European Medicines Agency approvals, which are methodologically not test-bound.

Details

Original languageEnglish
Article numbere2300348
Pages (from-to)1-12
Number of pages12
JournalJCO precision oncology
Volume8
Publication statusPublished - 21 Mar 2024
Peer-reviewedYes

External IDs

PubMed 38513168

Keywords

Sustainable Development Goals

ASJC Scopus subject areas