Étude des modifications génétiques des cancers de l’ovaire pour améliorer la prise en charge thérapeutique

Objectif(s) de la recherche et intérêt pour la santé publique

Finalité de l'étude

Objectifs poursuivis

Domaines médicaux investigués

Bénéfices attendus

High-grade serous ovarian carcinoma (HGSC) is characterized by extensive chromosomal instability and molecular heterogeneity. Current biomarker strategies mainly rely on the identification of homologous recombination deficiency (HRD), classifying tumors as HRD-positive or HRD-negative. However, this binary classification does not fully capture the biological diversity of HGSC, particularly among non-HRD tumors. Developing additional biomarkers able to better characterize these tumors could improve patient stratification and ultimately contribute to more personalized therapeutic strategies.

The objective of this project is to evaluate copy number (CN) signatures derived from shallow whole-genome sequencing (sWGS) as clinically relevant biomarkers in HGSC. Specifically, the study will assess the concordance between CN signature-based classification and the Myriad MyChoice HRD assay and explore the association of CN signatures with BRCA1/2 status and clinical outcomes.

The study will use existing clinical, pathological and genomic data from approximately 300 patients enrolled in the PAOLA-1 phase III clinical trial "Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB – IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance". Statistical analyses will evaluate their agreement with HRD status and investigate their relationship with progression-free survival, overall survival and other clinicopathological characteristics.