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Introduction/Background Despite the majority of BRCA1/2 mutated (BRCA1/2mut) ovarian carcinoma (OC) experience remarkably prolonged survival, the reason why some BRCA1/2mut carriers experience poor prognosis remains unclear, particularly for those patients who experience recurrence within 12 months following platinum-based chemotherapy. Furthermore, the advent of maintenance therapies from first-line settings, particularly PARP inhibitors (PARPi), has shifted the landscape of relapse, potentially reducing the incidence of true platinum-resistant recurrences. The identification of genetic and epigenetic differences may help to cluster patients at diagnosis and predict platinum response. Methodology We retrospectively enrolled 20 BRCA1/2mut FIGO stage III-IV HGSC patients, who received primary debulking surgery and adjuvant chemotherapy, regardless of maintenance therapy, between 2018 and 2022 at Fondazione Policlinico Universitario Agostino Gemelli. All samples were used for RNA extraction (QIAGEN RNeasy FFPE Kit). RNA concentrations were determined by the 260 nm absorbance, and purity was assessed based on the 260/280 nm ratio using NanoDropTM 2000 Spectrophotometer (ThermoFisher Scientific). RNA quality was checked by electrophoresis (Agilent TapeStation). The median RNA Integrity Number (RIN) was 6 (range 5.8–7.4) and therefore ribosomal depletion was performed. Indexed libraries were then processed (paired-end sequencing, 50M depth). EdgeR in R studio will be used for count files; both EnrichR and ShinyGO will be used for Gene Ontology. Additionally, part of the samples were tested for 523 multipanel genes' set through Next Generation Sequencing (NGS). Results We aim at identifying genes that may be uniquely over- or under-expressed among BRCA1/2mut patients with extreme prognostic outcomes. Additionally, we intend to integrate RNA sequencing data with those from NGS. Conclusion This integrated approach will enable us to describe molecular signatures that not only distinguish between patients with favorable and unfavorable prognoses but also enhance our understanding of the underlying mechanisms driving these diverse clinical outcomes. Disclosures R.E. reports Honoraria/consultation fees from GSK; C.M. reports Honoraria/consultation fees from AstraZeneca, Pharmamar, GSK, MSD, Menarini; A.F. reports Honoraria/consultation fees from AstraZeneca, MSD, Johnson G.S reports Honoraria/consultation fees from Covidien AG, AstraZeneca, MSD, Olympus Europa, Baxter Healthcare, GlaxoSmithKline, Intuitive Surgical Inc.; C.M. reports Honoraria/consultation fees from MSD, Illumina, GSK, Vedeva, Altems.
Ergasti et al. (Fri,) studied this question.