Genomic Instability Score Across Diverse Tumor Types Using the Illumina TruSight Oncology 500 HRD Assay

Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score ≥42, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation.