High Concordance of Different Assays in the Determination of Homologous Recombination Deficiency–Associated Genomic Instability in Ovarian Cancer-Reference-Cited by-同舟云学术

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

Published:2024-03 Issue:8 Volume: Page:
ISSN:2473-4284
Container-title:JCO Precision Oncology
language:en
Short-container-title:JCO Precis Oncol

Author:

Pfarr Nicole¹^ORCID,von Schwarzenberg Karin¹^ORCID,Zocholl Dario²^ORCID,Merkelbach-Bruse Sabine³,Siemanowski Janna³,Mayr Eva-Maria¹,Herold Sylvia⁴,Kleo Karsten⁵^ORCID,Heukamp Lukas C.⁶⁷,Willing Eva-Maria⁶⁷^ORCID,Menzel Michael⁸^ORCID,Lehmann Ulrich⁹^ORCID,Bartels Stephan⁹^ORCID,Chakraborty Shounak¹,Baretton Gustavo⁴,Demes Melanie C.¹⁰,Döring Claudia¹⁰^ORCID,Kazdal Daniel⁸^ORCID,Budczies Jan⁸,Rad Roland¹¹,Wild Peter¹⁰,Christinat Yann¹²^ORCID,McKee Thomas¹²^ORCID,Schirmacher Peter⁸,Horst David⁵^ORCID,Büttner Reinhard³^ORCID,Stenzinger Albrecht⁸,Sehouli Jalid⁷¹³,Vollbrecht Claudia⁵,Hummel Michael⁵,Braicu Elena I.⁷¹³¹⁴,Weichert Wilko¹,

Affiliation:

1. Institute of Pathology, School of Medicine and Health, Technical University Munich, Munich, Germany

2. Institute of Biometry and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, Berlin, Germany

3. Institute of Pathology, University Hospital Cologne, Cologne, Germany

4. Institute of Pathology, University Hospital Dresden, Dresden, Germany

5. Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin & Berlin Institute of Health, Berlin, Germany

6. Institute of Pathology and Hematopathology, Hamburg, Germany

7. North-Eastern German Society of Gynecological Oncology (NOGGO), Berlin, Germany

8. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

9. Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany

10. Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany

11. Institute of Functional Genomics, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany

12. Department of Pathology, University Hospital of Geneva, Geneva, Switzerland

13. Department of Gynecology, Campus Virchow Klinikum, Charité University Medicine, Berlin, Germany

14. Tumor Bank Ovarian Cancer Network (TOC) and Biostatistics, Charité Berlin, Berlin, Germany

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.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/PO.23.00348

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