Mp15-16 Molecular Characterization of Bladder Cancer Tumor Invasion Using Single-Cell Dna Sequencing

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP15)1 May 2024MP15-16 MOLECULAR CHARACTERIZATION OF BLADDER CANCER TUMOR INVASION USING SINGLE-CELL DNA SEQUENCING Benjamin I. Joffe, Clémentine Le Coz, Zejian Wang, John R. Christin, Caroline Laplaca, G. Joel DeCastro, Christopher B. Anderson, James M. McKiernan, Michael Shen, and Andrew T. Lenis Benjamin I. JoffeBenjamin I. Joffe , Clémentine Le CozClémentine Le Coz , Zejian WangZejian Wang , John R. ChristinJohn R. Christin , Caroline LaplacaCaroline Laplaca , G. Joel DeCastroG. Joel DeCastro , Christopher B. AndersonChristopher B. Anderson , James M. McKiernanJames M. McKiernan , Michael ShenMichael Shen , and Andrew T. LenisAndrew T. Lenis View All Author Informationhttps://doi.org/10.1097/01.JU.0001009500.87761.bf.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 20-30% of bladder cancer patients will have muscle-invasive disease (MIBC) at presentation. For those patients with non-muscle invasive bladder cancer (NMIBC), up to 30% will progress to MIBC (termed secondary MIBC). Compared to primary MIBC, secondary MIBC carries significantly worsened rates of cancer-related morbidity and mortality. The process of invasion is incompletely characterized and therefore no therapies target this process. We present the first characterization of the molecular landscape of tumor invasion using single-cell DNA sequencing (scDNA-seq). METHODS: Patients with suspected concurrent non-invasive and invasive tumors were identified and samples were obtained via cold-cup biopsy. Adjacent samples were sent separately for pathologic confirmation. Samples were processed into single nuclei for library creation and barcoding using the Tapestri single-cell instrument and sequenced. All data was processed using the Tapestri Pipeline software to generate single-cell genotypes and quantify clonal architecture of the paired invasive and non-invasive tumors. Additional patients with concurrent non-invasive and invasive bladder cancer are being identified, sequenced, and analyzed for comparison. RESULTS: One patient with pure squamous MIBC had scDNA-seq performed using samples from a pT3 tumor and area of non-invasive squamous carcinoma. scDNA-seq revealed expected mutational heterogeneity with alterations in several genes known to be associated with tumorigenesis of MIBC. Clinically-significant mutations accumulated in a stepwise fashion, with cells initially accumulating mutations in ARID1A, KMT2C, and PIK3CA, likely representing the development of MIBC. Subsequent copy-number neutral loss of heterozygosity (CNLOH) in KMT2C and ARID1A likely increase aggressive tumor biology. In contrast, the non-invasive carcinoma was genetically unrelated and had fewer mutations. CONCLUSIONS: Advanced sequencing modalities have allowed for improved characterization of MIBC. scDNA-seq identified multiple mutations in genes of interest ARID1A, KMT2C, and PIK3CA as involved in development of invasive phenotype. Further analysis will allow for better modeling of the stepwise nature of MIBC development. Download PPT Source of Funding: Maple Place Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e236 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Benjamin I. Joffe More articles by this author Clémentine Le Coz More articles by this author Zejian Wang More articles by this author John R. Christin More articles by this author Caroline Laplaca More articles by this author G. Joel DeCastro More articles by this author Christopher B. Anderson More articles by this author James M. McKiernan More articles by this author Michael Shen More articles by this author Andrew T. Lenis More articles by this author Expand All Advertisement PDF downloadLoading ...