Ovarian cancer (OC), specifically high-grade serous ovarian cancer (HGSOC), is characterized by deficiencies in homologous recombination (HR) [1]. Patients with germline (g) and somatic (s) BRCA1/2 pathogenic variants (PVs), genes that play a critical role in HR, are associated with improved survival [2,3] compared to those without PVs in BRCA1/2 or other HR genes, which we termed wildtype (WT) tumors. The former also derive clinical benefit from platinum-based therapies and targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors [4,5].

Germline PVs in genes other than BRCA1/2 associated with HR are also found in OC and HGSOC, and many, including RAD51C, RAD51D, BRIP1, and PALB2, have been associated with an increased risk of OC development, albeit to a lesser extent than BRCA1/2 [6]. The genomic landscape and HR signatures in these tumors as well as the survival outcomes of these patients compared to those with BRCA1/2-associated and WT OC is unknown.

We sought to comprehensively characterize the genomic landscape and measures of HR-deficiency (HRD) in OCs of patients with germline PVs in non-BRCA1/2 HR genes and evaluate clinical outcomes and survival compared to patients with g/s BRCA1/2-associated and WT tumors.