HOMOLOGOUS RECOMBINATION DEFICIENCY DETERMINATION IN PATIENTS WITH HIGH-GRADE SEROUS OVARIAN CANCER: REAL-WORD EXPERIENCE IN THE FRENCH CANCER INSTITUTE OF LORRAINE

Introduction/BackgroundDetermination of Homologous Recombination Deficiency (HRD) status has become crucial for the management of patients with high-grade serous ovarian carcinoma. Only patients with a proven HRD are prompt to benefit from treatment with a PARP inhibitor. Here we report a 6 months activity in our lab in Institut de Cancérologie de Lorraine, Nancy France.MethodologyFrom October 2022 to May 2023, we analysed 174 formalin-fixed embedded (FFPE) tissue samples from patients with ovarian cancer to determine the HRD status. All samples were qualified by a senior pathologist, DNA extracted using QIAmp FFPE kit and DNA concentration measured by fluorimetry. HRD status was determined using low-pass Whole Genome Sequencing and GIInger algorithm from Sophia Genetics. A 28-gene panel was also analysed for all samples within the same run on a NextSeq 550 instrument from illumina.ResultsAmong 174 samples, 153 were high-grade serous ovarian carcinoma (87.9%). Among 153 samples, HRD status was contributive for 135 (88.2%) and undetermined for 18 (11.8%). Among the 135 samples with a contributive result, 40.0% had a HRD status and 60.0% were proficient for HR (HRP). Among the 153 patients, 22 (14.4%) had a deleterious mutation of BRCA1 (15/22) or BRCA2 (7/22). A pathogenic mutation on TP53 gene were detectable in 145 out of 153 samples. Mutation with a class 3, 4 or 5 pathogenicity score was present in genes involved in HRR in 70/153 (45.7%) of the cases, but only 20/153 (13.0%) had a proven probably pathogenic or pathogenic validated mutation. Finally, CCNE amplification was detected in 30 patients (19.6%), 8 were HRD, 19 HRP and 3 undetermined).ConclusionIn conclusion, we present here a 6-month activity for HRD status determination in our Institute. Our results seem consistent with the literature and the assay we use able to identify accurately patients that might benefit PARP inhibitors.DisclosuresAlexandre Harlé received honoraria for presentation and expertise from GSK, AstraZeneca and Sophia Genetics. The other authors declare to have no disclosure.