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 d...

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Published in:	Nature communications Vol. 10; no. 1; pp. 3935 - 11
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 02-09-2019 Nature Publishing Group Nature Portfolio
Subjects:	45/23 45/91 631/67/1517/1709 631/67/69 Adenocarcinoma, Mucinous - classification Adenocarcinoma, Mucinous - genetics Adenocarcinoma, Mucinous - metabolism Benign Cancer Carcinoma, Ovarian Epithelial - classification Carcinoma, Ovarian Epithelial - genetics Carcinoma, Ovarian Epithelial - metabolism Cohort Studies Copy number Etiology Female Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Genetic analysis Humanities and Social Sciences Humans Invasiveness Menopause Metastases Metastasis multidisciplinary Mutation Organs Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - classification Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism p53 Protein Precursors Science Science (multidisciplinary) Sequence Analysis, DNA - methods Survival Analysis Taxonomy Tumors
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Summary:	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. Whether mucinous ovarian carcinoma (MOC) arises from cells at the ovary or from metastases from other primary sites is an unanswered question. Here, Cheasley et al perform a genetic analysis of the disease, showing that MOC arises at the ovary.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-11862-x