Journal article

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

Aritro Nath, Patrick Cosgrove, Benjamin Copeland, Hoda Mirsafian, Elizabeth Christie, Lance Pflieger, Sumana Majumdar, Mihaela Cristea, Ernest Han, Stephen Lee, Edward Wang, Sian Fereday, Nadia Traficante, Ravi Salgia, Theresa Werner, Adam Cohen, Phillip Moos, Jeffrey Chang, David Bowtell, Andrea Bild

CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2021

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..

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Grants

Awarded by NCI NIH HHS


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.