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 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

doi:10.1038/s41467-019-11862-x

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 FairweatherClare 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

Oncology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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 language	English (US)
Article number	3935
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11862-x
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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10.1038/s41467-019-11862-x

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Cheasley, D., Wakefield, M. J., Ryland, G. L., Allan, P. E., Alsop, K., Amarasinghe, K. C., Ananda, S., Anglesio, M. S., Au-Yeung, G., Böhm, M., Bowtell, D. D. L., Brand, A., Chenevix-Trench, G., Christie, M., Chiew, Y. E., Churchman, M., DeFazio, A., Demeo, R., Dudley, R., ... 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, 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

@article{8d04eccf40ad4b7790921b61e311a57b,

title = "The molecular origin and taxonomy of mucinous ovarian carcinoma",

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.}",

note = "Funding Information: This study was supported by the National Health and Medical Research Council of Australia (NHMRC) Grants #APP1045783 and #628434 and the Peter MacCallum Cancer Foundation. The authors acknowledge the Bioinformatics and Molecular Genomics Core Facilities of the Peter MacCallum Cancer Centre, which were supported by the Australian Cancer Research Foundation. We thank Sachintha Wijegu-nasekara and Ellen Gunn for technical assistance, and Margot Osinski (Royal Women{\textquoteright}s Hospital) for database assistance. The following cohorts were supported as follows: CASCADE: Supported by the Peter MacCallum Cancer Foundation. AOCS: 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, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of 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 Ovarian Cancer Australia and the Peter MacCallum Foundation. The AOCS also acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found at www.aocstudy.org. We would like to thank all of the women who participated in these research programs. COEUR: This study uses resources provided by the Canadian Ovarian Cancer Research Consortium{\textquoteright}s - COEUR biobank funded by the Terry Fox Research Institute and managed and supervised by the Centre hospi-talier de l{\textquoteright}Universit{\'e} de Montr{\'e}al (CRCHUM). The Consortium acknowledges contributions to its COEUR biobank from Institutions across Canada (for a full list see http://www.tfri.ca/en/research/translational-research/coeur/coeur_biobanks.aspx). The Gynaecological Oncology Biobank at Westmead is a member of the Australasian Biospecimen Network-Oncology group, which was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. OVCARE receives core funding from The BC Cancer Foundation and the VGH and UBC Hospital Foundation. Mayo Clinic: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation. Edinburgh: We extend our thanks to the Edinburgh Ovarian Cancer Database from which data were collected for this research and the Nicola Murray Foundation for supporting the Nicola Murray Centre for Ovarian Cancer Research. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-11862-x",

language = "English (US)",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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.

N1 - Funding Information: This study was supported by the National Health and Medical Research Council of Australia (NHMRC) Grants #APP1045783 and #628434 and the Peter MacCallum Cancer Foundation. The authors acknowledge the Bioinformatics and Molecular Genomics Core Facilities of the Peter MacCallum Cancer Centre, which were supported by the Australian Cancer Research Foundation. We thank Sachintha Wijegu-nasekara and Ellen Gunn for technical assistance, and Margot Osinski (Royal Women’s Hospital) for database assistance. The following cohorts were supported as follows: CASCADE: Supported by the Peter MacCallum Cancer Foundation. AOCS: 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, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of 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 Ovarian Cancer Australia and the Peter MacCallum Foundation. The AOCS also acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found at www.aocstudy.org. We would like to thank all of the women who participated in these research programs. COEUR: This study uses resources provided by the Canadian Ovarian Cancer Research Consortium’s - COEUR biobank funded by the Terry Fox Research Institute and managed and supervised by the Centre hospi-talier de l’Université de Montréal (CRCHUM). The Consortium acknowledges contributions to its COEUR biobank from Institutions across Canada (for a full list see http://www.tfri.ca/en/research/translational-research/coeur/coeur_biobanks.aspx). The Gynaecological Oncology Biobank at Westmead is a member of the Australasian Biospecimen Network-Oncology group, which was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. OVCARE receives core funding from The BC Cancer Foundation and the VGH and UBC Hospital Foundation. Mayo Clinic: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation. Edinburgh: We extend our thanks to the Edinburgh Ovarian Cancer Database from which data were collected for this research and the Nicola Murray Foundation for supporting the Nicola Murray Centre for Ovarian Cancer Research. Publisher Copyright: © 2019, The Author(s).

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.

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

U2 - 10.1038/s41467-019-11862-x

DO - 10.1038/s41467-019-11862-x

M3 - Article

C2 - 31477716

AN - SCOPUS:85071775939

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3935

ER -

The molecular origin and taxonomy of mucinous ovarian carcinoma

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