Journal article

19q12 amplified and non-amplified subsets of high grade serous ovarian cancer with overexpression of cyclin E1 differ in their molecular drivers and clinical outcomes

Diar Aziz, Dariush Etemadmoghadam, C Elizabeth Caldon, George Au-Yeung, Niantao Deng, Ryan Hutchinson, David Bowtell, Paul Waring

GYNECOLOGIC ONCOLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2018

Abstract

OBJECTIVES: Readily apparent cyclin E1 expression occurs in 50% of HGSOC, but only half are linked to 19q12 locus amplification. The amplified/cyclin E1hi subset has intact BRCA1/2, unfavorable outcome, and is potentially therapeutically targetable. We studied whether non-amplified/cyclin E1hi HGSOC has similar characteristics. We also assessed the expression of cyclin E1 degradation-associated proteins, FBXW7 and USP28, as potential drivers of high cyclin E1 expression in both subsets. METHODS: 262 HGSOC cases were analyzed by in situ hybridization for 19q12 locus amplification and immunohistochemistry for cyclin E1, URI1 (another protein encoded by the 19q12 locus), FBXW7 and USP28 express..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NHMRC


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


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


Awarded by Ovarian Cancer Research Program of the US Department of Defense


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

The authors acknowledge technical assistance, advice and support from Michael Christie, Irma Greshoff, Alisa Tubbs, Andrea Muranyi, Leanne Henricksen, Kandavel Shanmugam, Ruediger Ridder, Danielle Ferraro and Eric Walk. The Australian Ovarian Cancer Study (AOCS) acknowledges the cooperation of the participating institutions in Australia and the contribution of the study nurses, research assistants, and all clinical and scientific collaborators. We thank all of the women who participated in the study. This study was funded by a National Health and Medical Research Council (NHMRC) project grant (APP 1042358) and the NHMRC program grant (APP1092856). The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Cancer Council Queensland, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Council Western Australia (Multi -State Applications 191, 211 and 182) and the National Health and Medical Research Council of Australia (NHMRC; ID400413 and ID400281). The Australian Ovarian Cancer Study gratefully acknowledges additional support from S. Boldeman, the Agar family, Ovarian Cancer Action (UK), Ovarian Cancer Australia and the Peter MacCallum Foundation. Genotyping and immunohistochemistry staining of AOCS patient samples was supported by the Ovarian Cancer Research Program of the US Department of Defense (W81XWH-08-1-0684, W81XWH-08-1-0685); Cancer Australia and the National Breast Cancer Foundation (ID509303, CG-08-07, ID509366); the Peter MacCallum Cancer Centre Foundation and the Cancer Council Victoria. C. Elizabeth Caldon is supported by a National Breast Cancer Foundation Career Development Fellowship. Diar Aziz is a recipient of the Higher Committee of Education of Iraq Scholarship.