IntroductionHigh-grade serous ovarian carcinoma (HGSOC) is characterised by ubiquitous TP53 mutations and significant copy-number alterations. Current ctDNA assays for HGSOC have focused on detection of TP53 mutations. In patients with low-stage disease or during therapy, the amount of ctDNA may be below the threshold of reliable detection. We tested whether sensitivity for ctDNA detection could be increased by combining TP53 mutations with focal genomic amplifications.Material and methodsTargeted TP53 sequencing was performed on 264 plasma samples of 137 patients from the BriTROC-1 study with relapsed HGSOC tissue samples. Four patients had no somatic TP53 mutation detected and were excluded from analysis. Shallow WGS (0.1x) was performed on 256 plasma samples and matched tumour samples. The length-adjusted Z-score was calculated for each genomic segment and was used to distinguish significant focal amplifications (FA).Results and discussionsTP53 mutations were detected in 180 plasma samples with median mutant allele fraction (MAF) of 5% (IQR 1.4%–16%). Twenty-five patients had at least one plasma sample with MAF >20%, which could be used for genomic profiling.Focal amplifications were observed in 151 plasma samples with a median of 4 amplifications per sample. The FA with the maximum observed Z-score per sample was significantly correlated with TP53 MAF.Both approaches detected ctDNA in about half of the samples. However, in some plasma samples ctDNA could be detected only by one of the used methods.ConclusionCombining targeted TP53 sequencing with shallow WGS may be a more sensitive approach for ctDNA detection.