RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis

Aikaterini Tsantikidi; Konstantinos Papazisis; Theofanis Floros; Maria Gazouli; Eirini Papadopoulou; Georgios Tsaousis; Georgios Nasioulas; Andra Mester; Kubelac Paul Milan; Bogdan Gozman; Vlad Afrasanie; Dana Lucia Stanculeanu; Oana Trifanescu; Florentina Pescaru; Claudia Militaru; Christos Papadimitriou

doi:10.3892/ol.2023.14060

RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis

Oncol Lett. 2023 Sep 22;26(5):480. doi: 10.3892/ol.2023.14060. eCollection 2023 Nov.

Authors

Aikaterini Tsantikidi¹, Konstantinos Papazisis², Theofanis Floros³, Maria Gazouli⁴, Eirini Papadopoulou¹, Georgios Tsaousis¹, Georgios Nasioulas¹, Andra Mester⁵, Kubelac Paul Milan⁵, Bogdan Gozman⁶, Vlad Afrasanie⁶, Dana Lucia Stanculeanu⁷, Oana Trifanescu⁷, Florentina Pescaru⁸, Claudia Militaru⁹, Christos Papadimitriou¹⁰

Affiliations

¹ Genekor Medical S.A., Gerakas, 15344 Athens, Greece.
² Department of Oncology, Euromedica General Clinic, 54645 Thessaloniki, Greece.
³ Department of Oncology, Athens Naval and Veterans Hospital, 11521 Athens, Greece.
⁴ Department of Basic Medical Sciences National, Kapodistrian University of Athens, 11527 Athens, Greece.
⁵ Oncological Institute, 400015 Cluj-Napoca, Romania.
⁶ Regional Institute of Oncology, 700483 Iasi, Romania.
⁷ Bucharest Oncological Institute, 700483 Bucuresti, Romania.
⁸ St. Constantine Hospital, 500091 Brasov, Romania.
⁹ Medisprof Cluj-Napoca, 400641 Cluj-Napoca, Romania.
¹⁰ Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11528, Greece.

Abstract

Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type (BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment. In the present study, the performance of the Oncoscan CNV assay, accompanied by appropriate bioinformatic algorithms, was evaluated for its performance in GI calculation and was compared with that of a validated next-generation sequencing (NGS) test (myChoice HRD test). In addition, the clinical utility of the GI score (GIS) and BRCA1/2 tumor analysis were investigated in a cohort of 444 patients with ovarian cancer. For that reason, single nucleotide polymorphism (SNP) arrays and appropriate bioinformatics algorithms were used to calculate GIS in 29 patients with ovarian cancer with known GIS status using a validated NGS test. Furthermore, BRCA1/2 analysis results were compared between the aforementioned assay and the amplicon-based Oncomine^™ BRCA Research Assay. BRCA1/2 analysis was performed in 444 patients with ovarian cancer, while GIS was calculated in 175 BRCA1/2-negative cases. The bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis (RediScore), and the OncoscanR pipeline exhibited a high overall agreement with the validated test (93.1%). In addition, the Oncomine NGS assay had a 100% agreement with the validated test. The BRCA1/2 mutation frequency was 26.5% in the examined patients with ovarian cancer. GIS was positive in 40% of the BRCA1/2-negative cases. The RediScore bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in patients with ovarian cancer, offering a positive prediction for PARP inhibitor responsiveness in 55% of the patients.

Keywords: BRCA1; BRCA2; homologous recombination deficiency analysis; next generation sequencing; poly(ADP-ribose) polymerase 1 inhibitors; single nucleotide polymor-phism arrays.

Grants and funding

Funding: No funding was received.