Comprehensive genomic profiling (CGP) with loss of heterozygosity (LOH) to identify therapeutically relevant subsets of ovarian cancer (OC).

5512Background: Defective homologous recombination DNA repair (HRD) is associated with high grade serous (OC-S) histology, longer survival, and platinum (Pt) or PARP inhibitor (PARPi) sensitivity. HRD causes LOH, a pattern of allelic imbalance detectable by CGP. BRCAwt OC-S can have LOH and respond to PARPi, while non-serous (OC-NS) or difficult to classify (OC-NOS) OC are often less responsive to Pt-based therapy. Integrating multiple genomic features derived from CGP may define other therapeutically relevant subsets. Methods: DNA from FFPE tumor tissue obtained during clinical care for 4114 advanced OC was analyzed for all classes of genomic alterations (GA) by hybrid-capture, next-generation sequencing of up to 315 genes. Tumor subtype counts were OC-S, n = 2770; OC-NOS, n = 807; OC-NS, n = 537 (mucinous, clear cell, endometrioid, neuroendocrine, carcinosarcomas, and low grade serous). Algorithms evaluated microsatellite instability (MSI), tumor mutation burden (TMB; TMB-H ≥ 10 muts/Mb), and LOH (LOH-H...