Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

FAM Saner; K Takahashi; T Budden; A Pandey; D Ariyaratne; TA Zwimpfer; NS Meagher; S Fereday; L Twomey; KI Pishas; T Hoang; A Bolithon; N Traficante; K Alsop; EL Christie; EY Kang; GS Nelson; P Ghatage; CH Lee; MJ Riggan; J Alsop; MW Beckmann; J Boros; AH Brand; A Brooks-Wilson; ME Carney; P Coulson; M Courtney-Brooks; KL Cushing-Haugen; C Cybulski; MA El-Bahrawy; E Elishaev; R Erber; SA Gayther; A Gentry-Maharaj; C Blake Gilks; PR Harnett; HR Harris; A Hartmann; A Hein; J Hendley; BY Hernandez; A Jakubowska; M Jimenez-Linan; ME Jones; SH Kaufmann; CJ Kennedy; T Kluz; JM Koziak; B Kristjansdottir; ND Le; M Lener; J Lester; J Lubiński; C Mateoiu; S Orsulic; M Ruebner; MJ Schoemaker; M Shah; R Sharma; ME Sherman; YB Shvetsov; T Rinda Soong; H Steed; P Sukumvanich; A Talhouk; SE Taylor; RA Vierkant; C Wang; M Widschwendter; LR Wilkens; SJ Winham; MS Anglesio; A Berchuck; JD Brenton; I Campbell; LS Cook; JA Doherty; PA Fasching; RT Fortner; MT Goodman; J Gronwald; DG Huntsman; BY Karlan; LE Kelemen; U Menon; F Modugno; PDP Pharoah; JM Schildkraut; K Sundfeldt; AJ Swerdlow; EL Goode; A DeFazio; M Köbel; SJ Ramus; DDL Bowtell; DW Garsed

Journal article

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

FAM Saner, K Takahashi, T Budden, A Pandey, D Ariyaratne, TA Zwimpfer, NS Meagher, S Fereday, L Twomey, KI Pishas, T Hoang, A Bolithon, N Traficante, K Alsop, EL Christie, EY Kang, GS Nelson, P Ghatage, CH Lee, MJ Riggan Show all

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2024

DOI: 10.1158/1078-0432.CCR-23-3552

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Abstract

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alte..

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University of Melbourne Researchers

Julie Fereday Author

Kathleen Pishas Author

Nadia Traficante Author

Kathryn Alsop Author

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Awarded by Gottfried und Julia Bangerter-Rhyner-Stiftung

Funding Acknowledgements

We thank J. Beach and L. Bowes for their contributions to the study. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (1186505 to D.W. Garsed; 1092856, 1117044, and 2008781 to D.D.L. Bowtell; 2009840 to S.J. Ramus), the NIH/NCI (R01CA172404 to S.J. Ramus, P50 CA136393 to S.H. Kaufmann), and the US Army Medical Research and Materiel Command Ovarian Cancer Research Program (Award No. W81XWH-16-2-0010 and W81XWH-21-1-0401). DWG is supported by a Victorian Cancer Agency/Ovarian Cancer Australia Low-Survival Cancer Philanthropic Mid-Career Research Fellowship (MCRF22018). F.A.M. Saner is supported by a Swiss National Foundation Early Postdoc Mobility Fellowship (P2BEP3-172246), a Swiss Cancer League grant BIL KFS-3942-08-2016, the Foundation for Clinical-Experimental Cancer Research (Bern, Switzerland), and a Prof. Max Cloetta Foundation grant. K.I. Pishas is supported by an NHMRC CJ Martin Overseas Biomedical Fellowship (APP1111032). E.L. Christie is supported by a Victorian Cancer Agency Mid-Career Fellowship (MCRF21004). M. Widschwendter is supported by the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme grant agreement No 742432 (BRCA-ERC). K. Sundfeldt is supported by the Swedish Cancer Foundation. M.S. Anglesio is funded through a Michael Smith Health Research BC Scholar Award (18274) and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. BC's Gynecological Cancer Research team (OVCARE) receives support through the BC Cancer Foundation and the VGH & UBC Hospital Foundation. The Gynaecological Oncology Biobank at Westmead was funded by the NHMRC (ID310670 and ID628903) and the Cancer Institute NSW (12/RIG/1-17 and 15/RIG/1-16) and acknowledges support from the Department of Gynaecological Oncology, Westmead Hospital, and the Sydney West Translational Cancer Research Centre (Cancer Institute NSW 15/TRC/1-01). The Women's Cancer Research Program at Cedars-Sinai Medical Center (LAX) is supported by the National Center for Advancing Translational Sciences (NCATS) Grant UL1TR000124. The Study of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) is funded by Cancer Research UK (C490/A10119 C490/A10124 C490/A16561) and the UK NIH Research Biomedical Research Centre at the University of Cambridge. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) with a contribution to the authors' salary through MRC core funding MC_UU_00004/01 and the NIH Research University College London Hospitals Biomedical Research Centre. The investigators also acknowledge generous contributions from the Border Ovarian Cancer Awareness Group, the Peter MacCallum Cancer Foundation, the Graf Family Foundation, Wendy Taylor, Arthur Coombs and family, and the Piers K Fowler Fund. This article is dedicated to the memory of Prof. Naveena Singh. An anatomical pathologist specializing in gynecological cancer research, Prof. Singh made a significant contribution to the assessment and classification of tumor tissue samples in this study. She passed away in 2023.