Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer

A Nath; PA Cosgrove; H Mirsafian; EL Christie; L Pflieger; B Copeland; S Majumdar; MC Cristea; ES Han; SJ Lee; EW Wang; S Fereday; N Traficante; R Salgia; T Werner; AL Cohen; P Moos; JT Chang; DDL Bowtell; AH Bild

Journal article

Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer

A Nath, PA Cosgrove, H Mirsafian, EL Christie, L Pflieger, B Copeland, S Majumdar, MC Cristea, ES Han, SJ Lee, EW Wang, S Fereday, N Traficante, R Salgia, T Werner, AL Cohen, P Moos, JT Chang, DDL Bowtell, AH Bild

Nature Communications | Published : 2021

DOI: 10.1038/s41467-021-23171-3

Download PDF

Abstract

The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection of factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes of HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts to reveal that HGSOC is driven by three archetypal phenotypes, defined as oncogenic states that describe the majority of the transcriptome variation. Using a multi-task learning approach to identify the biological tasks of each archetype, we identify metabolism and proliferation..

View full abstract

University of Melbourne Researchers

Elizabeth Christie Author

Julie Fereday Author

Nadia Traficante Author

David Bowtell Author

Related Projects (5)

IMPROVING OUTCOMES FOR WOMEN WITH EPITHELIAL OVARIAN CANCER

THE MOLECULAR BIOLOGY OF HUMAN OVARIAN CANCER

The Fellowship would support Professor Bowtell, one of the world’s leading ovarian cancer researchers. His work focuses on clinical problems..

UNDERSTANDING AND TARGETING ACQUIRED CHEMORESISTANCE IN HIGH-GRADE SEROUS OVARIAN CANCER

We recently discovered a mutation in recurrent high-grade serous ovarian cancer that causes profound overexpression of the multidrug resista..

MOLECULAR AND SPATIAL CHARACTERIZATION OF DRUG RESISTANCE IN HUMAN OVARIAN CANCER

Ovarian cancer is the most deadly gynecologic cancer in Western women. Although initially responsive to chemotherapy, drug resistance common..

Molecular Epidemiology of Ovarian Research Institute

PUBLIC ABSTRACT A major obstacle to preventive strategies for ovarian cancer is the lack of recognized modifiable risk factors. Age, a pos..

Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This study was supported by a US National Cancer Institute U54 grant (U54CA209978) awarded to A.H.B., J.T.C., and D.D.L.B. D.D.L.B. is supported by National Health and Medical Research Council of Australia (NHMRC) grants APP1092856 and APP1117044. E.L.C. is supported by NHMRC grants APP1124309 and APP1161198. The Australian Ovarian Cancer Study (AOCS) was supported by the US Army Medical Research and Materiel Command under DAMD17-01-1-0729. We wish to thank Fred Adler, Mark Smithson, and members of the City of Hope U54 community for their invaluable feedback and support.