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 & 44 others 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 Le 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, Kylie L. Gorringe

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number3935
Number of pages11
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Cheasley, D., Wakefield, M. J., Ryland, G. L., Allan, P. E., Alsop, K., Amarasinghe, K. C., ... Gorringe, K. L. (2019). The molecular origin and taxonomy of mucinous ovarian carcinoma. Nature Communications, 10(1), [3935]. https://doi.org/10.1038/s41467-019-11862-x
Cheasley, Dane ; Wakefield, Matthew J. ; Ryland, Georgina L. ; Allan, Prue E. ; Alsop, Kathryn ; Amarasinghe, Kaushalya C. ; Ananda, Sumitra ; Anglesio, Michael S. ; Au-Yeung, George ; Böhm, Maret ; Bowtell, David D.L. ; Brand, Alison ; Chenevix-Trench, Georgia ; Christie, Michael ; Chiew, Yoke Eng ; Churchman, Michael ; DeFazio, Anna ; Demeo, Renee ; Dudley, Rhiannon ; Fairweather, Nicole ; Fedele, Clare G. ; Fereday, Sian ; Fox, Stephen B. ; Gilks, C. Blake ; Gourley, Charlie ; Hacker, Neville F. ; Hadley, Alison M. ; Hendley, Joy ; Ho, Gwo Yaw ; Hughes, Siobhan ; Hunstman, David G. ; Hunter, Sally M. ; Jobling, Tom W. ; Kalli, Kimberly R. ; Kaufmann, Scott H. ; Kennedy, Catherine J. ; Köbel, Martin ; Le Page, Cecile ; Li, Jason ; Lupat, Richard ; McNally, Orla M. ; McAlpine, Jessica N. ; Mes-Masson, Anne Marie ; Mileshkin, Linda ; Provencher, Diane M. ; Pyman, Jan ; Rahimi, Kurosh ; Rowley, Simone M. ; Salazar, Carolina ; Samimi, Goli ; Saunders, Hugo ; Semple, Timothy ; Sharma, Ragwha ; Sharpe, Alice J. ; Stephens, Andrew N. ; Thio, Niko ; Torres, Michelle C. ; Traficante, Nadia ; Xing, Zhongyue ; Zethoven, Magnus ; Antill, Yoland C. ; Scott, Clare L. ; Campbell, Ian G. ; Gorringe, Kylie L. / The molecular origin and taxonomy of mucinous ovarian carcinoma. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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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.",
author = "Dane Cheasley and Wakefield, {Matthew J.} and Ryland, {Georgina L.} and Allan, {Prue E.} and Kathryn Alsop and Amarasinghe, {Kaushalya C.} and Sumitra Ananda and Anglesio, {Michael S.} and George Au-Yeung and Maret B{\"o}hm and Bowtell, {David D.L.} and Alison Brand and Georgia Chenevix-Trench and Michael Christie and Chiew, {Yoke Eng} and Michael Churchman and Anna DeFazio and Renee Demeo and Rhiannon Dudley and Nicole Fairweather and Fedele, {Clare G.} and Sian Fereday and Fox, {Stephen B.} and Gilks, {C. Blake} and Charlie Gourley and Hacker, {Neville F.} and Hadley, {Alison M.} and Joy Hendley and Ho, {Gwo Yaw} and Siobhan Hughes and Hunstman, {David G.} and Hunter, {Sally M.} and Jobling, {Tom W.} and Kalli, {Kimberly R.} and Kaufmann, {Scott H.} and Kennedy, {Catherine J.} and Martin K{\"o}bel and {Le Page}, Cecile and Jason Li and Richard Lupat and McNally, {Orla M.} and McAlpine, {Jessica N.} and Mes-Masson, {Anne Marie} and Linda Mileshkin and Provencher, {Diane M.} and Jan Pyman and Kurosh Rahimi and Rowley, {Simone M.} and Carolina Salazar and Goli Samimi and Hugo Saunders and Timothy Semple and Ragwha Sharma and Sharpe, {Alice J.} and Stephens, {Andrew N.} and Niko Thio and Torres, {Michelle C.} and Nadia Traficante and Zhongyue Xing and Magnus Zethoven and Antill, {Yoland C.} and Scott, {Clare L.} and Campbell, {Ian G.} and Gorringe, {Kylie L.}",
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Cheasley, D, Wakefield, MJ, Ryland, GL, Allan, PE, Alsop, K, Amarasinghe, KC, Ananda, S, Anglesio, MS, Au-Yeung, G, Böhm, M, Bowtell, DDL, Brand, A, Chenevix-Trench, G, Christie, M, Chiew, YE, Churchman, M, DeFazio, A, Demeo, R, Dudley, R, Fairweather, N, Fedele, CG, Fereday, S, Fox, SB, Gilks, CB, Gourley, C, Hacker, NF, Hadley, AM, Hendley, J, Ho, GY, Hughes, S, Hunstman, DG, Hunter, SM, Jobling, TW, Kalli, KR, Kaufmann, SH, Kennedy, CJ, Köbel, M, Le Page, C, Li, J, Lupat, R, McNally, OM, McAlpine, JN, Mes-Masson, AM, Mileshkin, L, Provencher, DM, Pyman, J, Rahimi, K, Rowley, SM, Salazar, C, Samimi, G, Saunders, H, Semple, T, Sharma, R, Sharpe, AJ, Stephens, AN, Thio, N, Torres, MC, Traficante, N, Xing, Z, Zethoven, M, Antill, YC, Scott, CL, Campbell, IG & Gorringe, KL 2019, 'The molecular origin and taxonomy of mucinous ovarian carcinoma', Nature Communications, vol. 10, no. 1, 3935. https://doi.org/10.1038/s41467-019-11862-x

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

In: Nature Communications, Vol. 10, No. 1, 3935, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The molecular origin and taxonomy of mucinous ovarian carcinoma

AU - Cheasley, Dane

AU - Wakefield, Matthew J.

AU - Ryland, Georgina L.

AU - Allan, Prue E.

AU - Alsop, Kathryn

AU - Amarasinghe, Kaushalya C.

AU - Ananda, Sumitra

AU - Anglesio, Michael S.

AU - Au-Yeung, George

AU - Böhm, Maret

AU - Bowtell, David D.L.

AU - Brand, Alison

AU - Chenevix-Trench, Georgia

AU - Christie, Michael

AU - Chiew, Yoke Eng

AU - Churchman, Michael

AU - DeFazio, Anna

AU - Demeo, Renee

AU - Dudley, Rhiannon

AU - Fairweather, Nicole

AU - Fedele, Clare G.

AU - Fereday, Sian

AU - Fox, Stephen B.

AU - Gilks, C. Blake

AU - Gourley, Charlie

AU - Hacker, Neville F.

AU - Hadley, Alison M.

AU - Hendley, Joy

AU - Ho, Gwo Yaw

AU - Hughes, Siobhan

AU - Hunstman, David G.

AU - Hunter, Sally M.

AU - Jobling, Tom W.

AU - Kalli, Kimberly R.

AU - Kaufmann, Scott H.

AU - Kennedy, Catherine J.

AU - Köbel, Martin

AU - Le Page, Cecile

AU - Li, Jason

AU - Lupat, Richard

AU - McNally, Orla M.

AU - McAlpine, Jessica N.

AU - Mes-Masson, Anne Marie

AU - Mileshkin, Linda

AU - Provencher, Diane M.

AU - Pyman, Jan

AU - Rahimi, Kurosh

AU - Rowley, Simone M.

AU - Salazar, Carolina

AU - Samimi, Goli

AU - Saunders, Hugo

AU - Semple, Timothy

AU - Sharma, Ragwha

AU - Sharpe, Alice J.

AU - Stephens, Andrew N.

AU - Thio, Niko

AU - Torres, Michelle C.

AU - Traficante, Nadia

AU - Xing, Zhongyue

AU - Zethoven, Magnus

AU - Antill, Yoland C.

AU - Scott, Clare L.

AU - Campbell, Ian G.

AU - Gorringe, Kylie L.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071775939&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-11862-x

DO - 10.1038/s41467-019-11862-x

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3935

ER -

Cheasley D, Wakefield MJ, Ryland GL, Allan PE, Alsop K, Amarasinghe KC et al. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nature Communications. 2019 Dec 1;10(1). 3935. https://doi.org/10.1038/s41467-019-11862-x