Abstract:
Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT tumours, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) assay along with HRR function associated with CD8+ T-cell infiltration. Our study provides transcriptomic and phenotypic data highlighting temporal heterogeneity in HGSOCs and site-specific evolution of tumours in response to NACT which holds the potential to guide therapy selection.
Audience Take Away Notes:
- Understanding cancer heterogeneity in high grade serous ovarian cancers
- Transcriptomic and molecular analysis approaches to characterize tumours
