Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes

• DOI: 10.1016/j.xcrm.2023.101055
• Publication Date: 2023-05-22T14:44:35Z
• Authors: Paula Cunnea; Edward W. Curry; Elizabeth L. Chri...; Katherine Nixon; Chun Hei Kwok; Ahwan Pandey; Ratri Wulandari; Kerstin Thol; Jennifer Ploski; Cristina Morera-A...; Stephen McQuaid; Jingky Lozano-Kuehne; James J. Clark; Jonathan Krell; Euan A. Stronach; Iain A. McNeish; David D.L. Bowtell; Christina Fotopoulou
• Keywords: Spatial heterogeneity

Limited evidence exists on the impact of spatial and temporal heterogeneity high-grade serous ovarian cancer (HGSOC) tumor evolution, clinical outcomes, surgical operability. We perform systematic multi-site mapping at presentation matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler evolution. Three distinct evolutionary patterns primary to are identified, demonstrating recurrent disease may emerge pre-existing newly detected clones. Crucially, identify for clinically actionable homologous recombination deficiency scores poor prognosis biomarkers CCNE1 MYC. Copy-number signature, phenotypic, proteomic, proliferative-index further highlight HGSOC complexity. This study explores dissemination across space time, its optimal cytoreductive effort consequences decision-making.