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

Research output: Contribution to journalArticle

14 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 languageEnglish (US)
Article number3935
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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

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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