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The molecular origin and taxonomy of mucinous ovarian carcinoma


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.

Type Journal
ISBN 2041-1723
Authors Cheasley, D.; Wakefield, M. J.; Ryland, G. L.; Allan, P. E.; Alsop, K.; Amarasinghe, K. C.; Ananda, S.; Anglesio, M. S.; Au-Yeung, G.; Bohm, M.; Bowtell, D. D. L.; Brand, A.; Chenevix-Trench, G.; Christie, M.; Chiew, Y. E.; Churchman, M.; DeFazio, A.; Demeo, R.; Dudley, R.; Fairweather, N.; Fedele, C. G.; Fereday, S.; Fox, S. B.; Gilks, C. B.; Gourley, C.; Hacker, N. F.; Hadley, A. M.; Hendley, J.; Ho, G. Y.; Hughes, S.; Hunstman, D. G.; Hunter, S. M.; Jobling, T. W.; Kalli, K. R.; Kaufmann, S. H.; Kennedy, C. J.; Kobel, M.; Le Page, C.; Li, J.; Lupat, R.; McNally, O. M.; McAlpine, J. N.; Mes-Masson, A. M.; Mileshkin, L.; Provencher, D. M.; Pyman, J.; Rahimi, K.; Rowley, S. M.; Salazar, C.; Samimi, G.; Saunders, H.; Semple, T.; Sharma, R.; Sharpe, A. J.; Stephens, A. N.; Thio, N.; Torres, M. C.; Traficante, N.; Xing, Z.; Zethoven, M.; Antill, Y. C.; Scott, C. L.; Campbell, I. G.; Gorringe, K. L.
Responsible Garvan Author (missing name)
Publisher Name Nature Communications
Published Date 2019-09-02
Published Volume 10
Published Issue 1
Published Pages 3935
Status Always Electronic
DOI 10.1038/s41467-019-11862-x
URL link to publisher's version