Journal article

Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts

Monique D Topp, Lynne Hartley, Michele Cook, Valerie Heong, Emma Boehm, Lauren McShane, Jan Pyman, Orla McNally, Sumitra Ananda, Marisol Harrell, Dariush Etemadmoghadam, Laura Galletta, Kathryn Alsop, Gillian Mitchell, Stephen B Fox, Jeffrey B Kerr, Karla J Hutt, Scott H Kaufmann, Elizabeth M Swisher, David D Bowtell Show all

MOLECULAR ONCOLOGY | ELSEVIER SCI LTD | Published : 2014

Abstract

INTRODUCTION: Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models reflective of clinical responses. METHODS: We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγ(null) recipient mice, completed molecular annotation and assessed platinum sensitivity. RESULTS: The success rate of xenografting was 83%. Of ten HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and ..

View full abstract

Grants

Awarded by National Health and Medical Research Council (Fellowship JKF)


Awarded by National Health and Medical Research Council (Fellowship KJH)


Awarded by National Institute of Health


Awarded by U.S. Army Medical Research and Materiel Command


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported by fellowships and grants from the National Health and Medical Research Council (NHMRC Australia; Fellowships JKF (#441101), KJH (#494836)); the Cancer Council Victoria (Sir Edward Dunlop Fellowship in Cancer Research to CLS); the Victorian Cancer Agency (Clinical Fellowship to CLS); Monash University (PhD Scholarship to MT); CRC for Cancer Therapeutics (PhD top-up scholarship to MT), Ovarian Cancer Australia (PhD Scholarship to VH) and the National Institute of Health (2P50CA083636) (EMS) and the Wendy Feuer Ovarian Cancer Research Fund (EMS). This work was made possible through the Australian Cancer Research Foundation, the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. We thank Clovis Oncology for funding Foundation Medicine analyses. The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Tasmania and The Cancer Foundation of Western Australia and the National Health and Medical Research Council of Australia (NHMRC; ID400413). The Australian Ovarian Cancer Study gratefully acknowledges the cooperation of the participating institutions in Australia and also acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found at www.aocstudy.org. We would like to thank all of the women who participated in these research programs.