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

被引：19

作者：

Cunnea, Paula ^{[1
]}

Curry, Edward W. ^{[1
]}

Christie, Elizabeth L. ^{[2
,3
]}

Nixon, Katherine ^{[1
]}

Kwok, Chun Hei ^{[1
]}

Pandey, Ahwan ^{[2
]}

Wulandari, Ratri ^{[1
]}

Thol, Kerstin ^{[1
]}

Ploski, Jennifer ^{[1
]}

Morera-Albert, Cristina ^{[1
]}

McQuaid, Stephen ^{[4
]}

Lozano-Kuehne, Jingky ^{[5
]}

Clark, James J. ^{[1
]}

Krell, Jonathan ^{[1
]}

Stronach, Euan A. ^{[1
]}

McNeish, Iain A. ^{[1
]}

Bowtell, David D. L. ^{[2
,3
]}

Fotopoulou, Christina ^{[1
,6
]}

机构：

[1] Imperial Coll London, Dept Surg & Canc, Div Canc, London W12 0NN, England

[2] Peter Maallum Canc Ctr, Melbourne, Vic 3000, Australia

[3] Univ Melbourne, Sir Peter Maallum Dept Oncol, Melbourne, Vic 3010, Australia

[4] Queens Univ Belfast, Belfast BT7 1NN, North Ireland

[5] Imperial Coll London, Expt Canc Med Ctr, Dept Surg & Canc, London W12 0NN, England

[6] Imperial Coll NHS Trust, West London Gynaecol Canc Ctr, London W12 0HS, England

来源：

CELL REPORTS MEDICINE | 2023年 / 4卷 / 06期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

ADVANCED OVARIAN-CANCER; HOMOLOGOUS RECOMBINATION DEFICIENCY; GRADE SEROUS CARCINOMA; COPY NUMBER; QUALITY INDICATORS; EUROPEAN-SOCIETY; EXPRESSION; RECOMMENDATIONS; AMPLIFICATION; SURGERY;

D O I：

10.1016/j.xcrm.2023.101055

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：21

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