Year: 2016
Type: article
Study design: Observational Study
Abstract: You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2016MP88-13 MUTATIONAL LANDSCAPE OF PRIMARY BLADDER AND URACHAL ADENOCARCINOMA Byron Lee, Emmet Jordan, Helen Won, Aditya Bagrodia, Neil Desai, Dean Bajorin, Jonathan Rosenberg, Bernard Bochner, Wonkyu Kim, Michael Berger, David Solit, Hikmat Al-Ahmadie, and Gopa Iyer Byron LeeByron Lee More articles by this author , Emmet JordanEmmet Jordan More articles by this author , Helen WonHelen Won More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Neil DesaiNeil Desai More articles by this author , Dean BajorinDean Bajorin More articles by this author , Jonathan RosenbergJonathan Rosenberg More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Wonkyu KimWonkyu Kim More articles by this author , Michael BergerMichael Berger More articles by this author , David SolitDavid Solit More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , and Gopa IyerGopa Iyer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2431AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adenocarcinomas of the bladder and urachus represent a rare subtype of urinary tract cancer and account for 2% of all tumors originating from the bladder. Localized disease can be managed with surgical extirpation alone; however, less than 40% of patients with advanced disease will achieve an objective response with platinum-based chemotherapy. We hypothesized that bladder and urachal adenocarcinomas harbor a distinct mutational profile that may make them susceptible to targeted agents. METHODS After Institutional Review Board approval, 16 patients with primary bladder adenocarcinoma (PBA) and 10 patients with urachal adenocarcinoma (UA) were identified. Histopathologic review was performed, and tumor DNA isolated from representative paraffin-embedded sections as well as matched normal DNA were subjected to Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing, an exon-capture assay that interrogates the mutation and copy number status of 379 oncogenes and tumor suppressor genes known to be commonly altered in cancer. Somatic alterations including point mutations, insertions/deletions, truncations, and copy number changes were detected. RESULTS The study population consisted of 17 (65%) males and 9 (35%) females with local or locally advanced PBA or UA. 17 (65%) were ever smokers and 9 (35%) were never smokers. 4 (15%) patients received neoadjuvant chemotherapy, 14 (54%) underwent partial cystectomy, and 12 (46%) underwent radical cystectomy. Median overall survival was 41.2 months (95% CI: 12-129) in patients with PBA and 80.5 months (95% CI: 11-263) in patients with UA. Mutational analysis revealed that mutations resulting in upregulation of the mitogen-activated protein kinase (MAPK) pathway are common in PBA and UA (Table 1). CONCLUSIONS The mutational landscape of PBA and UA is more similar to that of colorectal adenocarcinoma than urothelial carcinoma of the bladder. Alterations predicted to upregulate the MAPK pathway such as activating KRAS and GNAS mutations are common in PBA and UA, and agents targeting this pathway may provide a novel therapeutic avenue for the treatment of PBA and UA. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1133-e1134 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Byron Lee More articles by this author Emmet Jordan More articles by this author Helen Won More articles by this author Aditya Bagrodia More articles by this author Neil Desai More articles by this author Dean Bajorin More articles by this author Jonathan Rosenberg More articles by this author Bernard Bochner More articles by this author Wonkyu Kim More articles by this author Michael Berger More articles by this author David Solit More articles by this author Hikmat Al-Ahmadie More articles by this author Gopa Iyer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2331253482