Mp15-18 Molecular Characterization of Urethral Cancer and Comparison With Bladder Cancer

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP15)1 May 2024MP15-18 MOLECULAR CHARACTERIZATION OF URETHRAL CANCER AND COMPARISON WITH BLADDER CANCER Fady Ghali, Patricia Galipeau, Michael Yang, Kim Dill-McFarland, Gavin Ha, R. Bruce Montgomery, Jonathan L. Wright, and Hung-Ming Lam Fady GhaliFady Ghali , Patricia GalipeauPatricia Galipeau , Michael YangMichael Yang , Kim Dill-McFarlandKim Dill-McFarland , Gavin HaGavin Ha , R. Bruce MontgomeryR. Bruce Montgomery , Jonathan L. WrightJonathan L. Wright , and Hung-Ming LamHung-Ming Lam View All Author Informationhttps://doi.org/10.1097/01.JU.0001009500.87761.bf.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urethral cancer (UC) is a rare clinical entity that can occur as a primary tumor of the urethra, or concurrently with bladder cancer (BC). The molecular underpinnings of urethral cancer remains unknown. We sought to perform molecular characterization of paired primary UC, secondary UC, and paired BC tumors. METHODS: Patients that underwent surgery for BC and /or UC were retrospectively identified. They were grouped as follows: group 1 was primary UC, group 2 was UC associated with BC, and group 3 represents paired BC samples. Transcriptome and whole-exome sequencing was performed from formalin-fixed paraffin embedded UC/BC samples. Gene level abundance was quantified. Consensus molecular subclassification, gene set enrichment (GSEA), tumor microenvironment (TME), and copy number variation (CNV) analysis were also performed. RESULTS: Tissue from 19 patients with BC/UC was isolated and analyzed: six in group one, eight in group 2, and five in group 3. Exact-match shared mutations were more common between groups 2 and 3, than group 1 (Figure 1A), yet all three groups demonstrated unique mutations (Figure 1B). RNA-seq analysis identified 431 differentially expressed genes (DEG), and GSEA identified several pro-inflammatory pathways upregulated in BC, while E2F/Myc pathways were upregulated in UC (Figure 2). TME demonstrated enrichment of multiple inflammatory cells and markers within group 1 compared to groups 2/3. CNV identified distinct differences but suggested shared origin between Groups 2 and 3. CONCLUSIONS: We present a comprehensive molecular characterization of primary UC, and paired UC/BC tumors. Our findings suggest a likely shared origin between UC and BC in patients that have bladder and urethral cancer. Still, unique tumor alterations exist. Primary UC is significantly more inflammatory compared with the other groups. Download PPTDownload PPT Source of Funding: Seattle Translational Tumor Research (to HML), Howard Cohen Foundation (to JLW), Department of Defense (W81XWH-19-1-0624 to HML) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e237 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Fady Ghali More articles by this author Patricia Galipeau More articles by this author Michael Yang More articles by this author Kim Dill-McFarland More articles by this author Gavin Ha More articles by this author R. Bruce Montgomery More articles by this author Jonathan L. Wright More articles by this author Hung-Ming Lam More articles by this author Expand All Advertisement PDF downloadLoading ...