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.

Details

Title
The molecular origin and taxonomy of mucinous ovarian carcinoma
Author
Cheasley, Dane 1   VIAFID ORCID Logo  ; Wakefield, Matthew J 2   VIAFID ORCID Logo  ; Ryland, Georgina L 1   VIAFID ORCID Logo  ; Allan, Prue E 1 ; Alsop, Kathryn 3 ; Amarasinghe, Kaushalya C 1   VIAFID ORCID Logo  ; Ananda, Sumitra 4 ; Anglesio, Michael S 5   VIAFID ORCID Logo  ; Au-Yeung, George 3 ; Böhm, Maret 6 ; Bowtell, David D L 3 ; Brand, Alison 7 ; Chenevix-Trench, Georgia 8 ; Christie, Michael 9 ; Yoke-Eng Chiew 7 ; Churchman, Michael 10 ; DeFazio, Anna 7   VIAFID ORCID Logo  ; Demeo, Renee 1 ; Dudley, Rhiannon 11 ; Fairweather, Nicole 11 ; Fedele, Clare G 3 ; Fereday, Sian 3   VIAFID ORCID Logo  ; Fox, Stephen B 3   VIAFID ORCID Logo  ; C Blake Gilks 5 ; Gourley, Charlie 10   VIAFID ORCID Logo  ; Hacker, Neville F 12 ; Hadley, Alison M 13 ; Hendley, Joy 1 ; Ho, Gwo-Yaw 14   VIAFID ORCID Logo  ; Hughes, Siobhan 1 ; Hunstman, David G 5 ; Hunter, Sally M 1 ; Jobling, Tom W 15 ; Kalli, Kimberly R 16 ; Kaufmann, Scott H 16   VIAFID ORCID Logo  ; Kennedy, Catherine J 7   VIAFID ORCID Logo  ; Köbel, Martin 17   VIAFID ORCID Logo  ; Cecile Le Page 18   VIAFID ORCID Logo  ; Li, Jason 1 ; Lupat, Richard 1 ; McNally, Orla M 19 ; McAlpine, Jessica N 5   VIAFID ORCID Logo  ; Mes-Masson, Anne-Marie 20 ; Mileshkin, Linda 1 ; Provencher, Diane M 21 ; Pyman, Jan 22 ; Rahimi, Kurosh 21 ; Rowley, Simone M 1 ; Salazar, Carolina 1 ; Samimi, Goli 6 ; Saunders, Hugo 1 ; Semple, Timothy 1 ; Sharma, Ragwha 23 ; Sharpe, Alice J 24 ; Stephens, Andrew N 11   VIAFID ORCID Logo  ; Thio, Niko 1 ; Torres, Michelle C 1   VIAFID ORCID Logo  ; Traficante, Nadia 3 ; Xing, Zhongyue 1 ; Zethoven, Magnus 1 ; Antill, Yoland C 25 ; Scott, Clare L 26   VIAFID ORCID Logo  ; Campbell, Ian G 3   VIAFID ORCID Logo  ; Gorringe, Kylie L 3   VIAFID ORCID Logo 

1  Peter MacCallum Cancer Centre, Melbourne, Australia 
2  Walter and Eliza Hall Institute, Parkville, Australia; The University of Melbourne, Melbourne, Australia 
3  Peter MacCallum Cancer Centre, Melbourne, Australia; The University of Melbourne, Melbourne, Australia 
4  Peter MacCallum Cancer Centre, Melbourne, Australia; Western Health, St. Albans, Australia 
5  University of British Columbia, Vancouver, Canada 
6  Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Australia 
7  Westmead Hospital, University of Sydney, Sydney, Australia 
8  Queensland Institute of Medical Research, Brisbane, Australia 
9  The University of Melbourne, Melbourne, Australia; Royal Melbourne Hospital, Parkville, Australia 
10  Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Edinburgh Centre, University of Edinburgh, Edinburgh, UK 
11  Hudson Institute of Medical Research, Clayton, Australia 
12  The University of New South Wales, Sydney, Australia 
13  Royal Brisbane and Womens Hospital, Brisbane, Australia 
14  Walter and Eliza Hall Institute, Parkville, Australia 
15  Monash Medical Centre, Clayton, Australia 
16  Mayo Clinic, Rochester, MN, USA 
17  The University of Calgary, Calgary, Canada 
18  CRCHUM, Montreal, Canada 
19  The University of Melbourne, Melbourne, Australia; Royal Womens Hospital, Parkville, Australia 
20  CRCHUM, Montreal, Canada; University of Montreal, Montreal, Canada 
21  CRCHUM, Montreal, Canada; Centre Hospitalier de L’Université de Montreal, Montreal, Canada 
22  Royal Womens Hospital, Parkville, Australia; Royal Children’s Hospital, Flemington, Australia 
23  Westmead Hospital, University of Sydney, Sydney, Australia; NSW Health Pathology, Sydney, Australia 
24  Monash University, Clayton, Australia 
25  Cabrini Health, Malvern, Australia; Frankston Hospital, Frankston, Australia 
26  Peter MacCallum Cancer Centre, Melbourne, Australia; Walter and Eliza Hall Institute, Parkville, Australia; The University of Melbourne, Melbourne, Australia; Royal Melbourne Hospital, Parkville, Australia 
Pages
1-11
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11862-x
ProQuest document ID
2283282438
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.