TY - JOUR
T1 - Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes
AU - Cunnea, Paula
AU - Curry, Edward W
AU - Christie, Elizabeth L
AU - Nixon, Katherine
AU - Kwok, Chun Hei
AU - Pandey, Ahwan
AU - Wulandari, Ratri
AU - Thol, Kerstin
AU - Ploski, Jennifer
AU - Morera-Albert, Cristina
AU - McQuaid, Stephen
AU - Lozano-Kuehne, Jingky
AU - Clark, James J
AU - Krell, Jonathan
AU - Stronach, Euan A
AU - McNeish, Iain A
AU - Bowtell, David D L
AU - Fotopoulou, Christina
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - cytoreductive surgery
KW - HRD
KW - spatial and temporal heterogeneity
KW - tumor evolution
KW - Cyclin E1
KW - high-grade serous ovarian cancer
KW - homologous recombination deficiency score
U2 - 10.1016/j.xcrm.2023.101055
DO - 10.1016/j.xcrm.2023.101055
M3 - Article
C2 - 37220750
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 6
M1 - 101055
ER -