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  • #1056 Multi-omic characterization of naïve treatment samples of epithelial ovarian cancer addressed to neoadjuvant chemotherapy: an hypothesis-generating study on biomarkers of response to platinum-based chemotherapy

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11. Translational Research/Biomarkers
#1056 Multi-omic characterization of naïve treatment samples of epithelial ovarian cancer addressed to neoadjuvant chemotherapy: an hypothesis-generating study on biomarkers of response to platinum-based chemotherapy
  1. Rita Trozzi1,
  2. Luca Mastrantoni2,3,
  3. Camilla Nero1,4,
  4. Simona Duranti5,
  5. Valentina Iacobelli1,
  6. Angelo Minucci6,
  7. Tina Pasciuto7,
  8. Luciano Giacò8,
  9. Gian Franco Zannoni1,
  10. Diana Giannarelli9,
  11. Domenica Lorusso1,
  12. Maria De Bonis6,
  13. Claudia Marchetti1,4,
  14. Anna Fagotti1,4 and
  15. Giovanni Scambia1,4
  1. 1Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  2. 2UOC Oncologia medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  3. 3Università Cattolica del Sacro Cuore, Rome, Italy
  4. 4Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
  5. 5Scientific Directorate, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  6. 6Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  7. 7Data Collection Research Core Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  8. 8Bioinformatics Research Core Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  9. 9Biostatistics Unit, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Rome, Italy

Abstract

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.

Abstract #1056 Figure 1
Abstract #1056 Figure 1

https://doi.org/10.1136/ijgc-2024-ESGO.1122

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