PD01-08 COMPARISON OF MUTATIONAL PROFILE OF PRIMARY VERSUS ORGAN-SPECIFIC METASTATIC TUMORS IN CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 May 2022PD01-08 COMPARISON OF MUTATIONAL PROFILE OF PRIMARY VERSUS ORGAN-SPECIFIC METASTATIC TUMORS IN CLEAR CELL RENAL CELL CARCINOMA Sari Khaleel, Renzo DiNatale, Benjamin Freeman, Ritesh Kotecha, Robert Motzer, Paul Russo, Jonathan Coleman, Eduard Reznik, and Ari Hakimi Sari KhaleelSari Khaleel More articles by this author , Renzo DiNataleRenzo DiNatale More articles by this author , Benjamin FreemanBenjamin Freeman More articles by this author , Ritesh KotechaRitesh Kotecha More articles by this author , Robert MotzerRobert Motzer More articles by this author , Paul RussoPaul Russo More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Eduard ReznikEduard Reznik More articles by this author , and Ari HakimiAri Hakimi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002516.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While the mutational profile (MP) of primary clear cell renal cell carcinoma has been well described, the MP of metastatic ccRCC tumors remain less clear, particularly for organ-specific metastases. We sought to compare the MP of primary tumors to organ-specific metastases in ccRCC. METHODS: Targeted next generation sequencing data comprising the MPs of 417 primary and 217 unmatched metastatic ccRCC specimens were retrieved from our institutional database. Differentially mutated genes (DMGs) in metastatic relative to primary specimens were identified, as well as DMGs for the cohort’s 4 most common metastatic sites. We then repeated our analysis focusing on mutations with a corresponding estimated cancer cell fraction (CCF) of ≥ 90% in their tissue specimen, suggesting that these mutations are pervasive clonal mutations of higher clinical relevance. Analyses were performed using R v4.0.4 (The R Foundation for Statistical Computing). RESULTS: Primary tumors had significantly higher tumor purity (TP) and lower mutational burden (TMB) compared to metastases (51.3% vs 47.36%, p=0.049; 56.4 vs 67.2 mutations/Mb, p<0.001, respectively). Relative to primary tumors, the top 3 DMGs in all-metastases were SETD2, PTEN, and KMT2D (adjusted Fisher p-value<0.05). The top 4 metastatic sites were lung, bone, brain, and adrenal, with a distinct set of DMGs for each site, although none reached statistical significance (p>0.05; Table 1). Focusing on samples with mutational CCF ≥90% reduced our cohort size to 284 primary and 130 metastatic tumors, with no statistically significant changes from the original cohort’s age, gender, TP or TMB distributions. Relative to primary tumors, the top DMG profile in all-metastases remained unchanged in this subcohort, with some differences in the DMG profile of site-specific metastases, although none reached statistical significance (p>0.05). CONCLUSIONS: Mutational profiles of ccRCC vary between primary and metastatic tumors, and among different metastatic tumor organ sites. This could have potential downstream implications for the prognosis and therapeutic response of these tumors, as their response to targeted therapies may be affected by the genomic context of their background tissue. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e32 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sari Khaleel More articles by this author Renzo DiNatale More articles by this author Benjamin Freeman More articles by this author Ritesh Kotecha More articles by this author Robert Motzer More articles by this author Paul Russo More articles by this author Jonathan Coleman More articles by this author Eduard Reznik More articles by this author Ari Hakimi More articles by this author Expand All Advertisement PDF downloadLoading ...