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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 17 Publications

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	Sequencing data for Australian Ovarian Cancer study submitted 20121116	AB SOLiD 4 System	72
EGAD00001000877	Complete WGS and RNA-Seq dataset for Australian ICGC ovarian cancer sequencing project 2014-07-07, representing 93 donors. Sequencing was performed on Illumina HiSeq. Alignment of the lane-level fastq data was performed with bwa (WGS data) and RSEM (transcriptome data). For this dataset lane-level .bam files have been merged and de-duplicated to create a single bam file for each sample type (tumour/normal) for each donor. This dataset supersedes all previous datasets for this study. 2016-08-08 updated with 14 outstanding RNA-seq samples & corresponding RSEM bams 2016-12-07 updated with 7 outstanding RNA-seq controls and corresponding RSEM bams		331

Publications	Citations
Whole-genome characterization of chemoresistant ovarian cancer. Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS, Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD. Nature 521: 2015 489-494	879
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. Tanwar DK, Parker DJ, Gupta P, Spurlock B, Alvarez RD, Basu MK, Mitra K. Oncotarget 7: 2016 60021-60037	55
Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer. O'Donnell T, Christie EL, Ahuja A, Buros J, Aksoy BA, Bowtell DDL, Snyder A, Hammerbacher J. BMC Cancer 18: 2018 87	23
Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer. Hillman RT, Chisholm GB, Lu KH, Futreal PA. J Natl Cancer Inst 110: 2018 None	18
Expression of the POTE gene family in human ovarian cancer. Barger CJ, Zhang W, Sharma A, Chee L, James SR, Kufel CN, Miller A, Meza J, Drapkin R, Odunsi K, Klinkebiel D, Karpf AR. Sci Rep 8: 2018 17136	18
Epigenetic activation of POTE genes in ovarian cancer. Sharma A, Albahrani M, Zhang W, Kufel CN, James SR, Odunsi K, Klinkebiel D, Karpf AR. Epigenetics 14: 2019 185-197	14
Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer. Christie EL, Pattnaik S, Beach J, Copeland A, Rashoo N, Fereday S, Hendley J, Alsop K, Brady SL, Lamb G, Pandey A, deFazio A, Thorne H, Bild A, Bowtell DDL. Nat Commun 10: 2019 1295	86
Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer. Qi X, Yu C, Wang Y, Lin Y, Shen B. Clin Transl Med 8: 2019 28	21
Co-regulation and function of FOXM1/RHNO1 bidirectional genes in cancer. Barger CJ, Chee L, Albahrani M, Munoz-Trujillo C, Boghean L, Branick C, Odunsi K, Drapkin R, Zou L, Karpf AR. Elife 10: 2021 e55070	15
Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer. Pishas KI, Cowley KJ, Pandey A, Hoang T, Beach JA, Luu J, Vary R, Smith LK, Shembrey CE, Rashoo N, White MO, Simpson KJ, Bild A, Griffiths JI, Cheasley D, Campbell I, Bowtell DDL, Christie EL. Cancers (Basel) 13: 2021 5644	2
Involvement of Cancer Stem Cells in Chemoresistant Relapse of Epithelial Ovarian Cancer Identified by Transcriptome Analysis. Sun Y, Yao L, Wang C, Xiong B, Guo J, Wang L, Zhu J, Cheng Z, Liu S. J Oncol 2022: 2022 6406122	2
The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer. Garsed DW, Pandey A, Fereday S, Kennedy CJ, Takahashi K, Alsop K, Hamilton PT, Hendley J, Chiew YE, Traficante N, Provan P, Ariyaratne D, Au-Yeung G, Bateman NW, Bowes L, Brand A, Christie EL, Cunningham JM, Friedlander M, Grout B, Harnett P, Hung J, McCauley B, McNally O, Piskorz AM, Saner FAM, Vierkant RA, Wang C, Winham SJ, Pharoah PDP, Brenton JD, Conrads TP, Maxwell GL, Ramus SJ, Pearce CL, Pike MC, Nelson BH, Goode EL, DeFazio A, Bowtell DDL. Nat Genet 54: 2022 1853-1864	34
Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology. MacDonald S, Foley H, Yap M, Johnston RL, Steven K, Koufariotis LT, Sharma S, Wood S, Addala V, Pearson JV, Roosta F, Waddell N, Kondrashova O, Trzaskowski M. Sci Rep 13: 2023 7395	0
Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis. Salamini-Montemurri M, Lamas-Maceiras M, Lorenzo-Catoira L, Vizoso-Vázquez Á, Barreiro-Alonso A, Rodríguez-Belmonte E, Quindós-Varela M, Cerdán ME. 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. Saner FAM, Takahashi K, Budden T, Pandey A, Ariyaratne D, Zwimpfer TA, Meagher NS, Fereday S, Twomey L, Pishas KI, Hoang T, Bolithon A, Traficante N, Australian Ovarian Cancer Study Group, Alsop K, Christie EL, Kang EY, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Alsop J, Beckmann MW, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, El-Bahrawy MA, Elishaev E, Erber R, Gayther SA, Gentry-Maharaj A, Gilks CB, Harnett PR, Harris HR, Hartmann A, Hein A, Hendley J, Hernandez BY, Jakubowska A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Kluz T, Koziak JM, Kristjansdottir B, Le ND, Lener M, Lester J, Lubiński J, Mateoiu C, Orsulic S, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Soong TR, Steed H, Sukumvanich P, Talhouk A, Taylor SE, Vierkant RA, Wang C, Widschwendter M, Wilkens LR, Winham SJ, Anglesio MS, Berchuck A, Brenton JD, Campbell I, Cook LS, Doherty JA, Fasching PA, Fortner RT, Goodman MT, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sundfeldt K, Swerdlow AJ, Goode EL, DeFazio A, Köbel M, Ramus SJ, Bowtell DDL, Garsed DW. Clin Cancer Res 30: 2024 3481-3498	1
Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer. Burdett NL, Willis MO, Pandey A, Twomey L, Alaei S, Australian Ovarian Cancer Study Group, Bowtell DDL, Christie EL. Nat Commun 15: 2024 6069	2
High-level tumour methylation of <i>BRCA1</i> and <i>RAD51C</i> is required for homologous recombination deficiency in solid cancers. Xu L, Liddell B, Nesic K, Geissler F, Ashwood LM, Wakefield MJ, Scott CL, Waddell N, Kondrashova O. NAR Cancer 6: 2024 zcae033	1