Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: implications for surgical and clinical outcomes
Author(s)
Type
Journal Article
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.
Date Issued
2023-06-20
Date Acceptance
2023-04-28
Citation
Cell Reports Medicine, 2023, 4 (6), pp.1-20
ISSN
2666-3791
Publisher
Elsevier
Start Page
1
End Page
20
Journal / Book Title
Cell Reports Medicine
Volume
4
Issue
6
Copyright Statement
© 2023 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37220750
PII: S2666-3791(23)00169-6
Subjects
Cyclin E1
cytoreductive surgery
high-grade serous ovarian cancer
homologous recombination deficiency score
HRD
spatial and temporal heterogeneity
tumor evolution
Publication Status
Published
Coverage Spatial
United States
Article Number
101055
Date Publish Online
2023-05-22