The molecular origin and taxonomy of mucinous ovarian carcinoma

Dane Cheasley, Matthew J. Wakefield, Georgina L. Ryland, Prue E. Allan, Kathryn Alsop, Kaushalya C. Amarasinghe, Sumitra Ananda, Michael S. Anglesio, George Au-Yeung, Maret Böhm, David D. L. Bowtell, Alison Brand, Georgia Chenevix-Trench, Michael Christie, Yoke-Eng Chiew, Michael Churchman, Anna DeFazio, Renee Demeo, Rhiannon Dudley, Nicole Fairweather, Clare G. Fedele, Sian Fereday, Stephen B. Fox, C Blake Gilks, Charlie Gourley, Neville F. Hacker, Alison M. Hadley, Joy Hendley, Gwo-Yaw Ho, Siobhan Hughes, David G. Hunstman, Sally M. Hunter, Tom W. Jobling, Kimberly R. Kalli, Scott H. Kaufmann, Catherine J. Kennedy, Martin Köbel, Cecile Page, Jason Li, Richard Lupat, Orla M. McNally, Jessica N. McAlpine, Anne-Marie Mes-Masson, Linda Mileshkin, Diane M. Provencher, Jan Pyman, Kurosh Rahimi, Simone M. Rowley, Carolina Salazar, Goli Samimi, Hugo Saunders, Timothy Semple, Ragwha Sharma, Alice J. Sharpe, Andrew N. Stephens, Niko Thio, Michelle C. Torres, Nadia Traficante, Zhongyue Xing, Magnus Zethoven, Yoland C. Antill, Clare L. Scott, Ian G. Campbell and Kylie L. Gorringe ()
Additional contact information
Dane Cheasley: Peter MacCallum Cancer Centre
Matthew J. Wakefield: Walter and Eliza Hall Institute
Georgina L. Ryland: Peter MacCallum Cancer Centre
Prue E. Allan: Peter MacCallum Cancer Centre
Kathryn Alsop: Peter MacCallum Cancer Centre
Kaushalya C. Amarasinghe: Peter MacCallum Cancer Centre
Sumitra Ananda: Peter MacCallum Cancer Centre
Michael S. Anglesio: University of British Columbia
George Au-Yeung: Peter MacCallum Cancer Centre
Maret Böhm: Kinghorn Cancer Centre and Garvan Institute of Medical Research
David D. L. Bowtell: Peter MacCallum Cancer Centre
Alison Brand: University of Sydney
Georgia Chenevix-Trench: Queensland Institute of Medical Research
Michael Christie: The University of Melbourne
Yoke-Eng Chiew: University of Sydney
Michael Churchman: University of Edinburgh
Anna DeFazio: University of Sydney
Renee Demeo: Peter MacCallum Cancer Centre
Rhiannon Dudley: Hudson Institute of Medical Research
Nicole Fairweather: Hudson Institute of Medical Research
Clare G. Fedele: Peter MacCallum Cancer Centre
Sian Fereday: Peter MacCallum Cancer Centre
Stephen B. Fox: Peter MacCallum Cancer Centre
C Blake Gilks: University of British Columbia
Charlie Gourley: University of Edinburgh
Neville F. Hacker: The University of New South Wales
Alison M. Hadley: Royal Brisbane and Womens Hospital
Joy Hendley: Peter MacCallum Cancer Centre
Gwo-Yaw Ho: Walter and Eliza Hall Institute
Siobhan Hughes: Peter MacCallum Cancer Centre
David G. Hunstman: University of British Columbia
Sally M. Hunter: Peter MacCallum Cancer Centre
Tom W. Jobling: Monash Medical Centre
Kimberly R. Kalli: Mayo Clinic
Scott H. Kaufmann: Mayo Clinic
Catherine J. Kennedy: University of Sydney
Martin Köbel: The University of Calgary
Cecile Page: CRCHUM
Jason Li: Peter MacCallum Cancer Centre
Richard Lupat: Peter MacCallum Cancer Centre
Orla M. McNally: The University of Melbourne
Jessica N. McAlpine: University of British Columbia
Anne-Marie Mes-Masson: CRCHUM
Linda Mileshkin: Peter MacCallum Cancer Centre
Diane M. Provencher: CRCHUM
Jan Pyman: Royal Womens Hospital
Kurosh Rahimi: CRCHUM
Simone M. Rowley: Peter MacCallum Cancer Centre
Carolina Salazar: Peter MacCallum Cancer Centre
Goli Samimi: Kinghorn Cancer Centre and Garvan Institute of Medical Research
Hugo Saunders: Peter MacCallum Cancer Centre
Timothy Semple: Peter MacCallum Cancer Centre
Ragwha Sharma: University of Sydney
Alice J. Sharpe: Monash University
Andrew N. Stephens: Hudson Institute of Medical Research
Niko Thio: Peter MacCallum Cancer Centre
Michelle C. Torres: Peter MacCallum Cancer Centre
Nadia Traficante: Peter MacCallum Cancer Centre
Zhongyue Xing: Peter MacCallum Cancer Centre
Magnus Zethoven: Peter MacCallum Cancer Centre
Yoland C. Antill: Cabrini Health
Clare L. Scott: Peter MacCallum Cancer Centre
Ian G. Campbell: Peter MacCallum Cancer Centre
Kylie L. Gorringe: Peter MacCallum Cancer Centre

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases.

Date: 2019
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DOI: 10.1038/s41467-019-11862-x

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