You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2018PD46-02 CARCINOMAS OF THE RENAL MEDULLA: A COMPREHENSIVE GENOMIC PROFILING (CGP) STUDY Stephanie Gleicher, Clarissa Cassol, Joseph Jacob, Oleg Shapiro, Julie Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Vincent A. Miller, Philip J. Stephens, Laurie M. Gay, Dmitra Bourboulia, Mehdi Mollapour, Jeffrey S. Ross, and Gennady Bratslavsky Stephanie GleicherStephanie Gleicher More articles by this author , Clarissa CassolClarissa Cassol More articles by this author , Joseph JacobJoseph Jacob More articles by this author , Oleg ShapiroOleg Shapiro More articles by this author , Julie Andrea ElvinJulie Andrea Elvin More articles by this author , Jo-Anne VergilioJo-Anne Vergilio More articles by this author , James SuhJames Suh More articles by this author , Shakti RamkissoonShakti Ramkissoon More articles by this author , Siraj Mahamed AliSiraj Mahamed Ali More articles by this author , Alexa Betzig SchrockAlexa Betzig Schrock More articles by this author , Vincent A. MillerVincent A. Miller More articles by this author , Philip J. StephensPhilip J. Stephens More articles by this author , Laurie M. GayLaurie M. Gay More articles by this author , Dmitra BourbouliaDmitra Bourboulia More articles by this author , Mehdi MollapourMehdi Mollapour More articles by this author , Jeffrey S. RossJeffrey S. Ross More articles by this author , and Gennady BratslavskyGennady Bratslavsky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2150AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) represent rare tumors that arise in the renal medulla and are therapy resistant with rapid progression. The objective of this study is to better define the genomic profile of these tumors. METHODS DNA was extracted from 40 microns of FFPE specimen from refractory CDC (46 cases) and RMC (24 cases). CGP was performed using a hybrid-capture, adaptor ligation based next generation sequencing assay to a mean coverage depth of >800X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. Microsatellite instability status (MSI) was determined on 114 loci. RESULTS All CDC patients were older and more frequently male (Table 1). Sickle cell trait was identified in both CDC and RMC, but far more frequently associated with RMC. All (100%) of CDC and RMC were clinically advanced Stage III and IV tumors with the primary tumor used for CGP in 70% of cases and a metastasis biopsy was sequenced in 30%. All (100%) CDC and RMC were intermediate (Grade 3) or high grade (Grade 4). In both tumor types, the rate of genetic alteration (GA) was relatively low and there were no (0%) VHL GA. SMARCB1 GA were significantly more frequent in RMC than CDC, but common in both tumors. Targeted therapies for kinase (EGFR, RET) and MTOR (NF2, TSC2) pathways were more frequent in CDC than RMC. At 1.8 mut/Mb, the median TMB was low for both tumor types with no (0%) cases showing = 20 mut/Mb. None (0%) of the CDC or RMC cases featured MSI-high status. CONCLUSIONS In addition to their histologic differences, the frequencies and types of GA seen in CDC differ significantly from that seen in RMC. The opportunities for biomarker driven targeted therapies for both CDC and RMC appear limited with rare opportunities to target GA in TKGFR and MTOR pathways for CDC. Similarly, the relatively low TMB and absence of MSI-High status in CDC and RMC also predicts that these tumors may be resistant to immunotherapies. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e891 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Stephanie Gleicher More articles by this author Clarissa Cassol More articles by this author Joseph Jacob More articles by this author Oleg Shapiro More articles by this author Julie Andrea Elvin More articles by this author Jo-Anne Vergilio More articles by this author James Suh More articles by this author Shakti Ramkissoon More articles by this author Siraj Mahamed Ali More articles by this author Alexa Betzig Schrock More articles by this author Vincent A. Miller More articles by this author Philip J. Stephens More articles by this author Laurie M. Gay More articles by this author Dmitra Bourboulia More articles by this author Mehdi Mollapour More articles by this author Jeffrey S. Ross More articles by this author Gennady Bratslavsky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...