You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II (PD39)1 Apr 2020PD39-05 PREVALENCE AND LANDSCAPE OF ACTIONABLE GENOMIC ALTERATIONS IN RENAL CELL CARCINOMA Kyrollis Attalla*, Renzo G. DiNatale, Eduard Reznik, Christopher Fong, Francisco Sanchez-Vega, Andrew W. Silagy, Stanley Weng, Jonathan Coleman, Chung-Han Lee, Maria I. Carlo, Paul Russo, Timothy A. Chan, Nikolaus D. Schultz, Martin H. Voss, and A. Ari Hakimi Kyrollis Attalla*Kyrollis Attalla* More articles by this author , Renzo G. DiNataleRenzo G. DiNatale More articles by this author , Eduard ReznikEduard Reznik More articles by this author , Christopher FongChristopher Fong More articles by this author , Francisco Sanchez-VegaFrancisco Sanchez-Vega More articles by this author , Andrew W. SilagyAndrew W. Silagy More articles by this author , Stanley WengStanley Weng More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Chung-Han LeeChung-Han Lee More articles by this author , Maria I. CarloMaria I. Carlo More articles by this author , Paul RussoPaul Russo More articles by this author , Timothy A. ChanTimothy A. Chan More articles by this author , Nikolaus D. SchultzNikolaus D. Schultz More articles by this author , Martin H. VossMartin H. Voss More articles by this author , and A. Ari HakimiA. Ari Hakimi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000918.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We report our experience with next-generation sequencing to characterize the prevalence and genomic landscape of actionable genomic alterations in renal cell carcinoma (RCC). METHODS: A query of our institutional clinical sequencing database was performed to include tumor samples sequenced across all cancers. Actionable alterations with clinical or biologic evidence supporting an association with response to targeted therapy were stratified by level of evidence using an oncology knowledge database (OncoKB). RESULTS: Data from 35,668 patients was included, and the 15 cancer types with the highest prevalence of actionable alterations were selected for subsequent analysis (28,027 patients). Of these cancers, RCC ranked 13th in prevalence of actionable alterations. Of 708 RCC samples included, 259 (37%) were from metastatic sites. However, of the remaining 449 primary samples, 208 (29%) belonged to patients who had metastatic disease at the time of sequencing. Although 81% of patients with any RCC harbored at least one known oncogenic mutation, only 90/687 (13%) harbored alterations for which compelling clinical data currently exist to justify the use of a standard or an investigational agent (levels of evidence 1 to 3B). This represents an increase from the previously reported prevalence (5% in 2017). The most common histologic subtype, clear cell RCC harbored the vast majority of actionable alterations, with 52/421 (12%) of clear cell RCC patients harboring at least one actionable alteration. Regarding the specific genes that harbor these alterations, 31 level 2A alterations were identified, all of which were TSC1/TSC2 mutations; 30 level 2B alterations were identified, of which PIK3CA (22) and BRCA1/BRCA2 (5) mutations were most common; 11 level 3A alterations, all of which were MTOR mutations, and 8 level 3B alterations, of which AKT1 (4) mutation was most common. CONCLUSIONS: Although the prevalence of actionable mutations in RCC seems to have doubled in recent years, the role of genetic testing in identifying candidates for targeted therapy in RCC is currently limited relative to other cancer types, emphasizing the need for additional research in this area to further inform targeted therapy decisions. Source of Funding: The Sidney Kimmel Center for Prostate and Urologic Cancers and in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e810-e810 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyrollis Attalla* More articles by this author Renzo G. DiNatale More articles by this author Eduard Reznik More articles by this author Christopher Fong More articles by this author Francisco Sanchez-Vega More articles by this author Andrew W. Silagy More articles by this author Stanley Weng More articles by this author Jonathan Coleman More articles by this author Chung-Han Lee More articles by this author Maria I. Carlo More articles by this author Paul Russo More articles by this author Timothy A. Chan More articles by this author Nikolaus D. Schultz More articles by this author Martin H. Voss More articles by this author A. Ari Hakimi More articles by this author Expand All Advertisement PDF downloadLoading ...