For individuals with ovarian cancer, therapy options mainly depend on BRCA1/2 germline status. As part of the observational AGO-TR1 study (NCT02222883), we conducted a paired blood/tumor analysis of 473 patients with ovarian cancer. Deleterious germline variants were found in 26.4% of the individuals, including BRCA1 and BRCA2. Tumor sequencing of the BRCA1, BRCA2, PIK3CA and PTEN genes along with BRCA1 and RAD51C promoter methylation analyses identified large subgroups of germline mutation-negative individuals who may be addressed in interventional studies using PARP or PI3K/AKT/mTOR inhibitors. (By Dr. rer. nat. Jan Hauke, https://jmg.bmj.com/content/early/2019/04/11/jmedgenet-2018-105930)