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

Paula Cunnea*, Edward W Curry, Elizabeth L Christie, Katherine Nixon, Chun Hei Kwok, Ahwan Pandey, Ratri Wulandari, Kerstin Thol, Jennifer Ploski, Cristina Morera-Albert, Stephen McQuaid, Jingky Lozano-Kuehne, James J Clark, Jonathan Krell, Euan A Stronach, Iain A McNeish, David D L Bowtell, Christina Fotopoulou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
33 Downloads (Pure)

Abstract

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 languageEnglish
Article number101055
JournalCell Reports Medicine
Volume4
Issue number6
Early online date22 May 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • cytoreductive surgery
  • HRD
  • spatial and temporal heterogeneity
  • tumor evolution
  • Cyclin E1
  • high-grade serous ovarian cancer
  • homologous recombination deficiency score

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