Abstract 1755: Integrative genomic and transcriptomic profiles from a prospective cervical cancer study (RAIDs)

Abstract Background: Cervical cancer (CC) remains a leading cause of gynecological cancer related mortality worldwide and constitutes the third most common malignancy in women. We have previously reported a “metagene” of genomic markers in the PI3K pathway and epigenetic regulators associated with poor outcome. Immune therapy recently showed promising results yet new biomarkers for targeted therapeutic approaches in this type of cancer remain to be determined. Patients 10mut/Mb) in 32/297 (11%) patients. The most frequent mutational signatures were APOBEC, deaminase and MMR (DNA mismatch repair deficiency (74%, 28% and 11% respectively). Interestingly, FGFR3 fusions were detected in 8/297 patients (3%). Transcriptomic analyses showed 510 differentially expressed genes between HPV positive and HPV negative CC (adjusted p-value0. 01 and |log2FC|1). No significantly differentially expressed genes were detected between FIGO 2018 stages (I/II vs III-IV). Both stages as well as tumor necrosis were highly significantly associated with progression-free survival (PFS), with tumor necrosis as an independent prognostic factor in a multivariable analysis (p0. 001). Presence or absence of CD8-positive lymphocytes, or CD68-positive cells of the myeloid cell compartment, histopathological subtype or number of TILs did not correlate with PFS. Conclusion: Our results confirm the high level of altered genes involved in chromatin remodeling with or without PI3K pathway mutations suggesting the relevance of epidrugs in CC. FGFR3 fusions and HRD tumors - although being rare (3%) - to be considered as new targeted approaches. Additionally, MSI and TMB high are of interest for immunotherapy beyond PD-L1 expression. Integrative analyses of omics and pathology data and correlation with PFS are ongoing and will be presented in the meeting. Citation Format: Maud Kamal, Solenn Barraud, Lolita Lecompte, Maral Halladjian, Emmanuelle Jeannot, Elodie Girard, Sylvain Baulande, Patricia Legoix, Fabrice Lecuru, Léa Pauly, Mathilde Saint-Ghislain, Stacy Cyrille, Célia Dupain, Constance Lamy, Olfa Chouchane-Mlik, Alexandra Oniga, Michel Mittelbronn, Christophe Le Tourneau, Aurélien Latouche, Nicolas Servant, Suzy Scholl, Ivan Bièche. Integrative genomic and transcriptomic profiles from a prospective cervical cancer study (RAIDs) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1755.