MP33-19 MOLECULAR CHARACTERISTICS AND ACTIONABLE TARGETS OF TESTICULAR GERM CELL TUMORS IN REAL-WORLD CONDITIONS

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP33-19 MOLECULAR CHARACTERISTICS AND ACTIONABLE TARGETS OF TESTICULAR GERM CELL TUMORS IN REAL-WORLD CONDITIONS Rafael Morales-Grimany, Cesar Delgado, Fady Baky, Armon Amini, Thomas Gerald, Rohit R Badia, Jacob Taylor, Luke L Wang, Juan Javier-Desloges, Vitaly Margulis, Solomon L. Woldu, Amir Salmasi, Fred Millard, Rana R. Mckay, and Aditya Bagrodia Rafael Morales-GrimanyRafael Morales-Grimany More articles by this author , Cesar DelgadoCesar Delgado More articles by this author , Fady BakyFady Baky More articles by this author , Armon AminiArmon Amini More articles by this author , Thomas GeraldThomas Gerald More articles by this author , Rohit R BadiaRohit R Badia More articles by this author , Jacob TaylorJacob Taylor More articles by this author , Luke L WangLuke L Wang More articles by this author , Juan Javier-DeslogesJuan Javier-Desloges More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Solomon L. WolduSolomon L. Woldu More articles by this author , Amir SalmasiAmir Salmasi More articles by this author , Fred MillardFred Millard More articles by this author , Rana R. MckayRana R. Mckay More articles by this author , and Aditya BagrodiaAditya Bagrodia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Molecular features of testicular germ cell tumors (GCT) in various clinical states (pre- vs post-chemotherapy, localized versus metastatic) may inform treatment options for patients with recurrence after definitive therapy. In his study, we describe molecular features and potential therapeutic targets in a cohort of patients with testicular GCT. METHODS: We retrospectively examined clinicopathologic and next-generation sequencing (NGS) data from 27 patients with GCT. Tumors were sequenced using the TempusxT solid tumor assay, which includes DNA sequencing of 595-648 genes at 500x coverage and RNA sequencing for all human coding genes. Tumor mutational burden (TMB) was measured for all tumors and PD-L1 levels were assessed qualitatively by 22C3 pharmDx immunohistochemistry assay in 8 patients. All genetic variants detected were quantified and analyzed to identify potentially actionable targets. RESULTS: We identified 13 (48%) stage I GCT, 11 (41%) stage II, and 3 (11%) stage III. There were 7 seminomas and 20 nonseminomas. 12 tumor specimen resections were obtained from orchiectomy, and 15 from retroperitoneal lymph node dissection (RPLND), of which, 8 were chemotherapy-naïve and 7 were post-chemotherapy. Chemo-naïve RPLND histology showed a combination of teratoma, seminoma, and mixed GCT, while post-chemo histology revealed 6 teratomas and 9 benign pathologies. The median TMB for the cohort was 0.75 mutations/megabase. Somatic mutations were identified in 55% of patients and most commonly within: KRAS (25.9%), KIT (11.1%), and PIK3CB (7.4%). PD-L1 expression was observed in 75% of the tumors measured (60% positivity at stage I and 100% positivity at stage III). Microsatellite stability was stable in 18 tumors tested. DNA alterations- [single base pair substitutions, insertions, and deletions]- in KRAS (GTPase) proto-oncogenes were detected in 7 tumors and tyrosine kinase receptor gene variants (KIT, P1K3CB) were found at similar frequencies across disease stages. Whole transcriptome NGS RNA expression assays were performed on 21 untreated specimens revealing overexpression of MTOR (33%), MAPK1(14%), and MET (8.0%). Actionable targets with FDA-approved therapies in other organ tissues were detected in 11 patients (40.7%). Incidental germline mutations, including MSH6, RB1, and MSH2, were identified in 9 patients though all were variants of unknown significance. CONCLUSIONS: In our study, a significant proportion of patients had potentially actionable molecular targets across the disease spectrum. The identified genetic alterations provide a genomic landscape for risk stratification, future therapies, and molecularly informed treatment paradigms for GCT patients. Source of Funding: Cancer Prevention and Research Institute © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e458 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rafael Morales-Grimany More articles by this author Cesar Delgado More articles by this author Fady Baky More articles by this author Armon Amini More articles by this author Thomas Gerald More articles by this author Rohit R Badia More articles by this author Jacob Taylor More articles by this author Luke L Wang More articles by this author Juan Javier-Desloges More articles by this author Vitaly Margulis More articles by this author Solomon L. Woldu More articles by this author Amir Salmasi More articles by this author Fred Millard More articles by this author Rana R. Mckay More articles by this author Aditya Bagrodia More articles by this author Expand All Advertisement PDF downloadLoading ...