MP16-17 GENOMIC LANDSCAPE OF METASTATIC HORMONE- NAÏVE PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP16)1 Apr 2020MP16-17 GENOMIC LANDSCAPE OF METASTATIC HORMONE- NAÏVE PROSTATE CANCER Kei Mizuno*, Shusuke Akamatsu, Takayuki Sumiyoshi, Takayuki Goto, Takashi Kobayashi, Toshinari Yamasaki, Takahiro Inoue, Akihiro Fujimoto, and Osamu Ogawa Kei Mizuno*Kei Mizuno* More articles by this author , Shusuke AkamatsuShusuke Akamatsu More articles by this author , Takayuki SumiyoshiTakayuki Sumiyoshi More articles by this author , Takayuki GotoTakayuki Goto More articles by this author , Takashi KobayashiTakashi Kobayashi More articles by this author , Toshinari YamasakiToshinari Yamasaki More articles by this author , Takahiro InoueTakahiro Inoue More articles by this author , Akihiro FujimotoAkihiro Fujimoto More articles by this author , and Osamu OgawaOsamu Ogawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000841.017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiple studies have demonstrated recurrent genomic alterations in advanced prostate cancer in recent years. However, genomic characterization of metastatic hormone-naïve prostate cancer (mHNPC) has been limited. Recently, we identified clinical parameters associated with prognosis in mHNPC, and it would be helpful to characterize genomic alterations in mHNPC for developing a more accurate prognostic model. In this study, we performed whole-exome sequencing (WES) of mHNPC and aimed to detect somatic genomic alterations and discover the relevance between the findings and clinical course. METHODS: Prostate biopsies were performed in 19 mHNPC patients and the specimens were halved. One section from each was used for pathological analysis, while the other was stored for DNA extraction. We extracted DNA from the stored section when the paired one had cancer cells, and matched germline DNA was isolated from blood. We then performed WES of DNA from tumor tissue and lymphocytes, and the following criteria were applied for variant calling: 1) variant allele frequency (VAF) of ≥ 5% after removing base calls with base quality or mapping quality of < 20; 2) the P-value of Fisher’s exact test comparing VAF in tumor to that in matched germline of < 0.001; 3) single nucleotide polymorphisms that were registered in databases were excluded. The relevance between genomic alterations and clinicopathological features were assessed. RESULTS: Of the 19 samples, five samples exhibited an exceptionally large number of somatic mutations, and the average tumor mutational burden (TMB) was 14.9 per megabase. The average TMB of the rest of 14 samples was 2.5 per megabase, which was about half that of castration-resistant prostate cancer. Of the five samples with high TMB, four had aberrations in DNA repair genes such as CDK12, ATM and ERCC2. Recurrently mutated genes were SPOP, FOXA1, KMT2C and ZMYM3, and all were mutated in five samples each. There was no relationship between TMB and clinicopathological features such as PSA progression-free survival, overall survival, PSA value and Gleason score. No specific mutation correlated with survival in this cohort. CONCLUSIONS: SPOP and FOXA1, which are key genes in AR signaling, were most frequently mutated in mHNPC. Patients with DNA repair genes mutations had higher TMB, which was not associated with worse survival in this study. Source of Funding: This study was supported by a research grant provided by Astellas Pharma. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e222-e222 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kei Mizuno* More articles by this author Shusuke Akamatsu More articles by this author Takayuki Sumiyoshi More articles by this author Takayuki Goto More articles by this author Takashi Kobayashi More articles by this author Toshinari Yamasaki More articles by this author Takahiro Inoue More articles by this author Akihiro Fujimoto More articles by this author Osamu Ogawa More articles by this author Expand All Advertisement PDF downloadLoading ...