Journal article

Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer

Elizabeth L Christie, Swetansu Pattnaik, Jessica Beach, Anthony Copeland, Nineveh Rashoo, Sian Fereday, Joy Hendley, Kathryn Alsop, Samuel L Brady, Greg Lamb, Ahwan Pandey, Anna deFazio, Heather Thorne, Andrea Bild, David DL Bowtell



ABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving ABCB1, placing it under the control of a strong promoter while leaving its open reading frame intact. We identified 15 different transcriptional fusion partners involving ABCB1, as well as patients with multiple distinct fusion events. The partner gene selected depended on its structure, promoter strength, and chromosomal proximity to ABCB1. Fusion positivity was strongly associated with the number of lines of MDR..

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Awarded by Department of Health and Human Services through the National Health and Medical Research Council of Australia (NHMRC)

Awarded by US National Cancer Institute U54 programme

Awarded by Victorian Cancer Agency

Awarded by Cancer Australia (CA)

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

Awarded by NHMRC


Funding Acknowledgements

This study was financially supported by grants from the Department of Health and Human Services through the National Health and Medical Research Council of Australia (NHMRC, APP631701 and APP1124309), the US National Cancer Institute U54 programme (U54CA209978), Victorian Cancer Agency (ECSG15012) and Cancer Australia (CA, APP1004673). We gratefully acknowledge additional support from Mrs. Margaret Rose AM and the Rose family, The WeirAnderson Foundation, Border Ovarian Cancer Awareness Group, donors to the Garvan Institute of Medical Research's Ovarian Cancer Research Programme, Wendy Taylor and Arthur Coombs and family. The Australian Ovarian Cancer Study (AOCS) was supported by the U.S. 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 NHMRC (ID400413 and ID400281). We acknowledge the vital role of the Australian Ovarian Cancer Study and kConFab for this study. AOCS acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Cancer Centre Foundation, and acknowledges the cooperation and contribution of the participating institutions in Australia and study nurses, research assistants and all clinical and scientific collaborators including Nadia Traficante, Linh Nguyen, Gillian Mitchell, Margot Osinski, Karen Sanday, Helen Steane and Leanne Bowes. The complete AOCS Study Group can be found at [].CASCADE acknowledges support from the Peter MacCallum Cancer Centre Foundation. We wish to thank Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study, which has received funding from the NHMRC, the National Breast Cancer Foundation (NBCF), CA, and the National Institute of Health (USA) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by a grant from the NBCF, and previously by the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. A. deFazio is supported by the University of Sydney Cancer Research Fund and Cancer Institute NSW, through the Sydney West Translational Cancer Research Centre. J. Beach was supported by the American Australian Association Sir Keith Murdoch Fellowship. We would like to thank all of the women who participated in the study.