Journal article

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)

Aline Talhouk, Joshy George, Chen Wang, Timothy Budden, Tuan Zea Tan, Derek S Chiu, Stefan Kommoss, Huei San Leong, Stephanie Chen, Maria P Intermaggio, Blake Gilks, Tayyebeh M Nazeran, Mila Volchek, Wafaa Elatre, Rex C Bentley, Janine Senz, Amy Lum, Veronica Chow, Hanwei Sudderuddin, Robertson Mackenzie Show all

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2020

Abstract

PURPOSE: Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sought to generate a clinical-grade minimal gene-set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene-expression data fr..

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Grants

Awarded by NIH


Awarded by United States Department of Defense Ovarian Cancer Research Program


Awarded by NIH/NCI


Awarded by European Union's Horizon 2020 European Research Council Programme, H2020 BRCA-ERC


Awarded by Cancer Australia


Awarded by American Cancer Society Early Detection Professorship


Awarded by National Center for Advancing Translational Sciences


Awarded by Canadian Institutes of Health Research


Awarded by National Health and Medical Research Council Enabling Grants


Awarded by Cancer Institute NSW Grants


Awarded by U.S. Army Medical Research and Materiel Command


Awarded by Cancer Foundation of Western Australia


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Ovarian Cancer Action


Awarded by Cancer Research UK


Awarded by National Institutes of Health/National Cancer Institute


Awarded by German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research


Funding Acknowledgements

We thank all the study participants who contributed to this study and all the researchers, clinicians, and technical and administrative staff who have made this work possible. This project received technical and data management support from OVCARE through the Cheryl Brown Ovarian Cancer Outcomes Unit and the Genetic Pathology Evaluation Centre. The AOV study recognizes the valuable contributions from Mie Konno, Shuhong Liu, Michelle Darago, Faye Chambers, and the staff at the Tom Baker Cancer Centre Translational Laboratories. The Australian Ovarian Cancer Study (AOCS) gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation. The AOCS also acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants, and all clinical and scientific collaborators to the study. The complete AOCS Group can be found at www.aocstudy.org.Furthermore, the authors thank Olivier Tredan and Pierre Heudel as investigators on the TRIO14 study and Sandrine Berge-Montamat as assistant for clinical research. Direct funding for this project was provided by the NIH (R01-CA172404, to principal investigator: S.J. Ramus; and R01-CA168758, to principal investigators: J.A. Doherty and M.A. Rossing), the Canadian Institutes for Health Research (Proof-ofPrinciple I program, to principal investigators: D.G. Huntsman and M.S. Anglesio), and the United States Department of Defense Ovarian Cancer Research Program (OC110433, to principal investigator: D.D. Bowtell). A. Talhouk was funded through a Michael Smith Foundation for Health Research Scholar Award. M.S. Anglesio was funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. J. George was partially supported by the NIH/NCI award number P30CA034196. In addition, other coauthor, biobanks, patient-recruitment studies, and programs received funding that has indirectly supported this work. C. Wang was a Career Enhancement Awardee of the Mayo Clinic SPORE in Ovarian Cancer (P50 CA136393). D.G. Huntsman received support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology and the Canada Research Chairs program (Research Chair in Molecular and Genomic Pathology). M. Widschwendter received funding from the European Union's Horizon 2020 European Research Council Programme, H2020 BRCA-ERC under grant agreement no. 742432, as well as the charity, The Eve Appeal (https://eveappeal.org.uk/), and support of the National Institute for Health Research and the University College London Hospitals Biomedical Research Centre. M.J. Henderson received funding from Cancer Australia (1067110). G.E. Konecny was supported by the Miriam and Sheldon Adelson Medical Research Foundation. B.Y. Karlan was funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences, grant UL1TR000124. H.R. Harris was supported by the NIH/NCI award number K22 CA193860. OVCARE (including the VAN study) received support through the BC Cancer Foundation and The VGHthornUBC Hospital Foundation (to authors A. Talhouk, B. Gilks, D.G. Huntsman, and M.S. Anglesio). The AOV study was supported by the Canadian Institutes of Health Research (MOP-86727).The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was funded by the National Health and Medical Research Council Enabling Grants ID 310670 and ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 and 15/RIG/1-16. The AOCS Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182), and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413; and ID400281). BriTROC-1 was funded by Ovarian Cancer Action (to I.A. McNeish and J.D. Brenton, grant number 006) and supported by Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274, and A19694) and the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres. Samples from the Mayo Clinic were collected and provided with support from the National Institutes of Health/National Cancer Institute P50 CA136393 (to E.L. Goode, G.L. Keeney, S.H. Kaufmann, and M.E. Sherman). Samples from the German Ovarian Cancer Study were collected and provided with support from the German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB9401), and the German Cancer Research Center (DKFZ).