| Autor: |
Cunnea, P, Curry, E, Christie, E, Nixon, K, Kwok, CH, Pandey, A, Wulandari, R, Thol, K, Ploski, J, Morera-Albert, C, McQuaid, S, Lozano-Kuehne, J, Clark, JJ, Krell, J, Stronach, E, McNeish, I, Bowtell, D, Fotopoulou, C |
| Rok vydání: |
2023 |
| Popis: |
Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumour evolution, clinical outcomes and surgical operability. We perform systematic multi-site tumour mapping at presentation and matched relapse from 49 high tumour burden patients, operated upfront. From SNP array-derived copy number data, we categorise dendrograms representing tumour clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favour simpler sympodial evolution. Three distinct tumour 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 highlights HGSOC complexity. This study explores HGSOC evolution and dissemination across space and time, its impact on optimal surgical cytoreductive effort and clinical outcomes, and consequences for clinical decision-making. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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