RediScore: Prospective Validation of a pipeline for Homologous Recombination Deficiency Analysis
Tumors harboring Homologous recombination deficiency (HRD) are considered optimal candidates for Poly (ADP-ribose)-polymerase 1 (PARP) inhibitors treatment. Such deficiency can be calculated by analysis of BRCA1/2 gene mutations, as well as by analysis of mutations in other genes of the Homologous recombination (HR) pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. In the present study, an assay for GI calculation was validated for its performance compared to an NGS validated assay. Moreover, the clinical utility of GI score (GIS) calculation and BRCA1/2 tumor analysis were investigated in a cohort of 444 Ovarian cancer patients.The RediScore bioinformatic algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in ovarian cancer patients, offering a positive prediction for PARPi responsiveness in 55% of the patients.