Journal article

Whole-genome characterization of chemoresistant ovarian cancer

Ann-Marie Patch, Elizabeth L Christie, Dariush Etemadmoghadam, Dale W Garsed, Joshy George, Sian Fereday, Katia Nones, Prue Cowin, Kathryn Alsop, Peter J Bailey, Karin S Kassahn, Felicity Newell, Michael CJ Quinn, Stephen Kazakoff, Kelly Quek, Charlotte Wilhelm-Benartzi, Ed Curry, Huei San Leong, Anne Hamilton, Linda Mileshkin Show all



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 observ..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Worldwide Cancer Research

Awarded by Cancer Australia

Awarded by US Army Medical Research and Materiel Command

Awarded by NHMRC

Awarded by Cancer Research UK

Awarded by Ovarian Cancer Action

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

The AOCS gratefully acknowledge the cooperation of the participating institutions in Australia, and also acknowledge the contribution of the study nurses, research assistants and all clinical and scientific collaborators including L. Galletta, C. Emmanuel, L. Bowes and J. Hallo. The authors acknowledge assistance from C. Anderson and D. Gwynne. The CASCADE investigators would like to thank the CASCADE Management Committee, all staff at the Victorian Institute of Forensic Medicine, D. Stevens and Tobin Brothers Funerals. The investigators would like to thank the Australia New Zealand Gynaecological Oncology Group (ANZGOG) and the women, and their families, who participated in these research programs. This work was supported by the National Health and Medical Research Council of Australia (NHMRC ID631701), Worldwide Cancer Research (09-0676) and Cancer Australia (1004673). The Australian Ovarian Cancer Study was supported by the US Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; ID400413, ID400281). The AOCS gratefully acknowledges additional support from S. Boldeman, the Agar family, Ovarian Cancer Australia and Ovarian Cancer Action (UK). The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was supported by grants from the NHMRC (ID 310670, ID628903) and the Cancer Institute of New South Wales. The CASCADE study was supported by the Peter MacCallum Cancer Centre Foundation, and in kind by the Victorian Institute of Forensic Medicine and Tobin Brothers Funerals.