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Genome Landscape of High-Grade Serous Ovarian Cancer

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001000293 AB SOLiD 4 System 72
EGAD00001000877 331
Publications Citations
Whole-genome characterization of chemoresistant ovarian cancer.
Nature 521: 2015 489-494
866
Crosstalk between the mitochondrial fission protein, Drp1, and the cell cycle is identified across various cancer types and can impact survival of epithelial ovarian cancer patients.
Oncotarget 7: 2016 60021-60037
53
Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer.
BMC Cancer 18: 2018 87
23
Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer.
J Natl Cancer Inst 110: 2018 None
18
Expression of the POTE gene family in human ovarian cancer.
Sci Rep 8: 2018 17136
18
Epigenetic activation of POTE genes in ovarian cancer.
Epigenetics 14: 2019 185-197
13
Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer.
Nat Commun 10: 2019 1295
82
Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer.
Clin Transl Med 8: 2019 28
21
Co-regulation and function of FOXM1/RHNO1 bidirectional genes in cancer.
Elife 10: 2021 e55070
14
Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer.
Cancers (Basel) 13: 2021 5644
1
Involvement of Cancer Stem Cells in Chemoresistant Relapse of Epithelial Ovarian Cancer Identified by Transcriptome Analysis.
J Oncol 2022: 2022 6406122
1
The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer.
Nat Genet 54: 2022 1853-1864
29
Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology.
Sci Rep 13: 2023 7395
0
Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.
Int J Mol Sci 24: 2023 10798
2
Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.
Clin Cancer Res 30: 2024 3481-3498
0
Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer.
Nat Commun 15: 2024 6069
0
High-level tumour methylation of <i>BRCA1</i> and <i>RAD51C</i> is required for homologous recombination deficiency in solid cancers.
NAR Cancer 6: 2024 zcae033
0