Fiche publication
Date publication
avril 2026
Journal
NPJ genomic medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KAMINSKY Marie-Christine
Tous les auteurs :
Blanc-Durand F, Yaniz Galende E, Ferron G, Kaminsky MC, Kalbacher E, Abadie-Lacourtoisie S, Joly F, Meunier J, Tredan O, Lebreton C, Alexandre J, Zannetti A, Louvet C, Blonz C, Dohollou N, Berton D, Desauw C, Carola E, Fabbro M, Follana P, Pujade-Lauraine E, Mourani L, Le Formal A, Gaultier De Saint Basile H, Genestie C, Rouleau E, Leary A
Lien Pubmed
Résumé
High-grade serous ovarian cancer (HGSOC) remains a leading cause of gynecological cancer mortality, with only <15% of patients achieving long-term, relapse-free survival. Using data from the VIVROVAIRE (NCT03418844) and CHIVA (NCT03418844) clinical trials, this study investigated the molecular and immunophenotypic characteristics of long-term recurrence-free survivors (LTS) compared with short-term survivors (STS). Tumor samples from 37 LTS (recurrence-free ≥3 years) and 105 STS were analyzed using next-generation sequencing, BRCA1/RAD51C promoter methylation assays, shallow whole genome and multiplex immunofluorescence. Homologous recombination deficiency (HRD) was defined by BRCA1/2 or RAD51C/D alterations, and genomic instability scores (GIS). Immune profiling included quantification of CD4, CD8, CD20, and FOXP3 cells. LTS were younger and had a lower prevalence of FIGO stage IV disease. Molecularly, LTS showed fewer TP53 mutations, enrichment of BRCA2 mutations and BRCA1 and RAD51C promoter methylation, and a strong association between RB1 loss co-occurring with a BRCA alteration. Conversely, CCNE1 amplification was underrepresented in LTS. Immune profiling demonstrated increased stromal and intraepithelial CD8 T-cell infiltration and reduced FOXP3 regulatory T cells in LTS. Overall, exceptional survival in HGSOC is associated with younger age, enrichment of BRCA2 mutations and BRCA1/RAD51C methylation, reduced CCNE1 amplification, and a competent antitumor immune response. These findings highlight potential biomarkers for refining risk stratification and guiding personalized therapeutic strategies in ovarian cancer management.
Référence
NPJ Genom Med. 2026 04 23;:
