MP06-03 RACE BASED DISPARITIES IN GENE EXPRESSION AND MUTATIONS IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2018MP06-03 RACE BASED DISPARITIES IN GENE EXPRESSION AND MUTATIONS IN BLADDER CANCER Kalen Rimar, Joshua Meeks, Sarah Psutka, and Edward Schaeffer Kalen RimarKalen Rimar More articles by this author , Joshua MeeksJoshua Meeks More articles by this author , Sarah PsutkaSarah Psutka More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.195AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES African Americans (AA) with urothelial carcinoma (UC) of the bladder have been shown to have worse cancer-specific (CSS) and overall survival (OS). Though several factors including socioeconomic status, access to care, and advanced stage at presentation have been proposed, the cause of this disparity remains undefined. Our objective was to compare bladder cancer gene expression and mutations between AA and Caucasian patients to assess whether the observed disparities in oncologic outcomes could be explained by associated mutational differences. METHODS Using the Bladder/Urothelial Carcinoma Cancer Genome Atlas (BC-TCGA, Provisional) we compared mutation type, frequency, signature, and gene expression between AA and Caucasian patients. We also compared differentially expressed genes according to race across all TCGA provisional cancer datasets that contained a minimum of 10 AA and 10 Caucasian patients per arm (19 of 33). RESULTS We identified 23 AA and 323 non-AA patients in the UC-TCGA dataset with available whole genome and RNA sequencing. There was no significant difference in the total mutation load between Caucasian and AA (range = 1 to 4472 variants/genome, n = 316, median = 240.5 vs. range = 82 to 562 variants/genome; n = 22, median=225.5, p=0.228). The majority of DNA substitution mutations in both Caucasian and AA patients were C->T, and there was no significant difference in frequency (p=0.33). There were no significant differences in Catalogue of Somatic Mutations in Cancer (COSMIC) signatures between the two groups (p=0.3). There was no significant difference in mutation frequency of known UC driver genes (TP53, MLL4, KDM6A, MLL3, PIK3CA, RB1, EP300, ERBB2) by race. Yet, we were able to identify 14 genes with significant differential expression according to race of which HIST1H2BD, L1TD1, and LRRC37A2 were associated with inferior OS (p<0.005, p=0.03, p=0.02). Notably, analyses of TCGA datasets revealed a conserved panel of genes differentially expressed by race across multiple cancers types involved in cell division and nucleosome function. CONCLUSIONS AA and Caucasians with UC have similar mutation type, frequency, and signature. However several differentially expressed genes within the UC were observed between AA and Caucasians and these differences remain consistent across many cancer types within the TCGA suggesting epigenetic regulation. Some of these gene expression differences may be independent of cancer. Nevertheless, the extent to which this differential gene expression may predispose to variable disease outcomes across race warrants further study. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e52-e53 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kalen Rimar More articles by this author Joshua Meeks More articles by this author Sarah Psutka More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...