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Introduction/Background The optimal surgical timing in patients with advanced epithelial ovarian cancer is still an open question, so patients to address neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) need to be carefully selected. A prognostic surrogate in patients undergoing IDS is the chemotherapy response score (CRS). We hypothesise that patients with good response (CRS3) vs scarce or no response (CRS1-2) could have a different genomic and gene expression profile. Methodology We performed a comprehensive genome profiling of 88 chemotherapy-naive advanced EOC patients addressed to NACT+IDS. We then performed a network analysis based on centrality measures. Moreover, we evaluated the gene expression profile by performing a bulk RNA sequencing analysis. Results TP53 emerged as the most mutated gene in the overall population. BRCA1 was mutated in 32% of CRS3 patients, mostly frameshift mutation insertion and splice site mutations, compared to 17% of CRS1-2 in which frameshift mutation deletions were the most common alteration. Similarly, PIK3CA showed missense mutations only in the CRS1-2 group. The network analysis in the CRS1-2 cohort revealed 18 genes co-altered with TP53 in at least 2% of the population. We appreciated a specific cluster involving FGF23, AKT2, PIK3CA, CCNE1 and KRAS among them. The CRS3 cohort displayed a higher number of co-altered genes (96), suggesting a more complex mutational landscape. We then restricted the analysis to those genes altered in at least 4% of the CRS3 population, obtaining a cluster between PTEN, BRCA1 and MYC. At the data cut-off of 06/01/2024, we successfully performed bulk RNA sequencing on 12 CRS 1-2 and 12 CRS 3. The total number of reads is 1.276.674.048, with 69.88% of clusters passing filters, and a%Q30 of 89.76. 66 samples are currently in sequencing. Conclusion CRS1-2 and CRS3 may exhibit distinct genomic landscapes. This study could pave the way for early characterization of patients' responses to platinum-based chemotherapy. Disclosures The presenting author has no disclosures.
Trozzi et al. (Fri,) studied this question.