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

Original publication

DOI

10.1016/j.xcrm.2023.101055

Type

Journal article

Journal

Cell reports. Medicine

Publication Date

06/2023

Volume

4

Addresses

Division of Cancer, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK. Electronic address: p.cunnea@imperial.ac.uk.

Keywords

Humans, Ovarian Neoplasms, Neoplasm Recurrence, Local, Proteomics, Female