Transcriptomics Can Predict Homologous Recombination Deficiency In Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers (MP60)1 Sep 2021MP60-02 TRANSCRIPTOMICS CAN PREDICT HOMOLOGOUS RECOMBINATION DEFICIENCY IN PROSTATE CANCER Adam Weiner, Yang Liu, Matthew McFarlane, Pushpinder Bawa, Eric Li, Xin Zhao, Ziwen Li, Tanya Hammoud, Munna Hazime, R. Jeffrey Karnes, Elai Davicioni, Zachery Reichert, Arul Chinnaiyan, Tamara Lotan, and Edward Schaeffer Adam WeinerAdam Weiner More articles by this author , Yang LiuYang Liu More articles by this author , Matthew McFarlaneMatthew McFarlane More articles by this author , Pushpinder BawaPushpinder Bawa More articles by this author , Eric LiEric Li More articles by this author , Xin ZhaoXin Zhao More articles by this author , Ziwen LiZiwen Li More articles by this author , Tanya HammoudTanya Hammoud More articles by this author , Munna HazimeMunna Hazime More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Zachery ReichertZachery Reichert More articles by this author , Arul ChinnaiyanArul Chinnaiyan More articles by this author , Tamara LotanTamara Lotan More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002095.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed and validated a transcriptomic signature for HRD in PCa (HRD-P). METHODS: By using an established mutational signature for tumor HRD, we created and validated a 16-gene signature for HRD-P in six independent PCa cohorts (primary PCa, n=8,224; metastatic castrate-resistant PCa [mCRPC], n=328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations that would have qualified patients for recent PARP inhibitor trials for mCRPC. RESULTS: HRD-P+ tumors were more numerous than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%; Figure 1) and mCRPC (126/328, 38% vs 82/328, 25%) cases and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with shorter time to recurrence following surgery and shorter overall survival in men with mCRPC (Figure 2). In a prospective trial of mCRPC treated with olaparib (n=10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. CONCLUSIONS: These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application. Source of Funding: This work was supported in part by the National Institutes of Health grant 5U01CA196390 (EMS), the Prostate Cancer Foundation (EMS), Department of Defense grant W81XWH-15-1-0661 (EMS and TLL), the 2019 Urology Care Foundation Residency Research Award Program and the Russell Scott, Jr., MD Urology Research Fund (ABW), as well as the University of Michigan Prostate Specialized Program of Research Excellence (SPORE) P50 CA186786-05 and the Early Detection Research Network grant UO1 CA111275 (AMC). © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1041-e1041 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Weiner More articles by this author Yang Liu More articles by this author Matthew McFarlane More articles by this author Pushpinder Bawa More articles by this author Eric Li More articles by this author Xin Zhao More articles by this author Ziwen Li More articles by this author Tanya Hammoud More articles by this author Munna Hazime More articles by this author R. Jeffrey Karnes More articles by this author Elai Davicioni More articles by this author Zachery Reichert More articles by this author Arul Chinnaiyan More articles by this author Tamara Lotan More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement Loading ...