Pd16-03 Understanding the Molecular Characteristics and Vulnerabilities of Sarcomatoid/Rhabdoid Renal Cell Carcinomas Through Integrative Histological and Spatial Genomics Approaches

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (PD16)1 May 2024PD16-03 UNDERSTANDING THE MOLECULAR CHARACTERISTICS AND VULNERABILITIES OF SARCOMATOID/RHABDOID RENAL CELL CARCINOMAS THROUGH INTEGRATIVE HISTOLOGICAL AND SPATIAL GENOMICS APPROACHES Mustafa Soytas, Tamiko Nishimura, Madeleine Arseneault, Eleonora Scarlata, Kate Glennon, Peixi Liu, Senthilkumar Kailasam, Fadi Brimo, Simon Tanguay, and Yasser Riazalhosseini Mustafa SoytasMustafa Soytas , Tamiko NishimuraTamiko Nishimura , Madeleine ArseneaultMadeleine Arseneault , Eleonora ScarlataEleonora Scarlata , Kate GlennonKate Glennon , Peixi LiuPeixi Liu , Senthilkumar KailasamSenthilkumar Kailasam , Fadi BrimoFadi Brimo , Simon TanguaySimon Tanguay , and Yasser RiazalhosseiniYasser Riazalhosseini View All Author Informationhttps://doi.org/10.1097/01.JU.0001009560.23593.56.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Genomic and immune analyses in S/R RCC have been limited to bulk tumor analysis and thus lack cellular resolution and spatial perspective. Herein, we use in situ Whole Transcriptome Profiling (WTP) to define molecular differences between tumor regions with and without S/R features, aiming at identifying molecular markers of S/R tumors that could lead to better diagnosis or treatments. METHODS: All patients who underwent surgical excision of RCC at the MUHC between 2010 and 2020 were screened by a uropathologist, and histologically defined regions of S/R, ccRCC, papillary, chromophobe RCC, and benign kidney were selected to construct tissue microarrays (TMAs). Whole-exome sequencing (WES) and Compartment-Guided Spatial WTP were applied for gene and transcriptome analysis (Figure 1). RESULTS: A cohort of 56 RCC patients and their TMAs, consisting of 403 cores representing patient-matched tumor areas with and without S/R features. For WES, 47 patients were used to identify copy number variations (CNVs) analysis. Four hundred cores of 55 patients were used for WTP and 5 groups of clustered with 2000 highly variable genes (HVGs) were constructed. The most variable genes of each tumor type were identified by using digital spatial transcriptome profiling (Figure 2). Whole-exome sequencing was used to identify mutational patterns of tumor cells using a list of specific genes of interest (Figure 3). CONCLUSIONS: According to current and ongoing results, WES, and compartment-guided WTP should be used to generate an unprecedented resolution to the molecular and genomic characteristics of S/R RCC tumors and tumor microenvironment. Download PPTDownload PPTDownload PPT Source of Funding: The Kidney Foundation of Canada © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e366 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Mustafa Soytas More articles by this author Tamiko Nishimura More articles by this author Madeleine Arseneault More articles by this author Eleonora Scarlata More articles by this author Kate Glennon More articles by this author Peixi Liu More articles by this author Senthilkumar Kailasam More articles by this author Fadi Brimo More articles by this author Simon Tanguay More articles by this author Yasser Riazalhosseini More articles by this author Expand All Advertisement PDF downloadLoading ...