EOC often display genomic heterogeneity and mutations associated with homologous recombination repair deficiency (HRD), which may have prognostic/predictive relevance. In the present study, we examined the mutational evolution in EOC and its association with patient outcome.
We examined coding mutations in 306 paraffin tissue samples from 69 patients with stage III-IV EOC treated with standard chemotherapy. The samples (2-9 per patient) were derived from normal salpinx epithelium (N), primary tumors (P) and metastatic sites (M). Coding regions in 39 EOC-related genes were sequenced at high depth (mean 2739; median 2362) and a genomic heterogeneity index (HGi) was calculated. Progression-free survival (PFS) was the clinical endpoint.
In 64/69 patients, at least 2 paired N, P and M samples shared 640 mutations (16% of all mutations) in 15 genes. Shared mutations (s-mut) exhibited higher allelic frequency as compared to private ones (all p
A temporal mutation order in the evolution of EOC is suggested; HRD mutations seem important in the transition from normal to primary tumor and TP53 mutations in metastatic spread. Genomic heterogeneity seems to interact with tumor histology and shared normal/tumor HRD mutations for patient prognosis. Validation in larger patient series is needed.
Clinical trial identification
Legal entity responsible for the study
Hellenic Cooperative Oncology Group
All authors have declared no conflicts of interest.