Combined Tumor-Based and Mutation Testing in Ovarian Cancer.

Somatic/germline mutations (m)/(likely) pathogenic variants (PV) (/) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic , combined tumor-based () and mutation testing () may improve the quality of results in somatic identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent testing. The ratio of allelic fractions (AFs) for was calculated to estimate the proportion of cells carrying and to infer LOH. Among the 142/237 results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) . Among the 195 contributive tumor samples, 43 DEL of (22.1%) were identified (23 and 20 with LOH identified in 37/41 conclusive samples. The median AF of was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both and , thus reidentifying them as . Combined testing is rapid, sensitive, and identifies somatic and germline AF is essential for interpreting in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of -related tumorigenesis.