Genomic Biomarkers for the Prediction of Stage and Prognosis of Upper Tract Urothelial Carcinoma
Year: 2016
Type: article
Study design: Observational Study
Abstract: PURPOSE: Genomic characterization of radical nephroureterectomy specimens in patients with upper tract urothelial carcinoma may allow for thoughtful integration of systemic and targeted therapies. We sought to determine whether genomic alterations in upper tract urothelial carcinoma are associated with adverse pathological and clinical outcomes. MATERIALS AND METHODS: Next generation exon capture sequencing of 300 cancer associated genes was performed in 83 patients with upper tract urothelial carcinoma. Genomic alterations were assessed individually and also grouped into core signal transduction pathways or canonical cell functions for association with clinicopathological outcomes. Binary outcomes, including grade (high vs low), T stage (pTa/T1/T2 vs pT3/T4) and organ confined status (pT2 or less and N0/Nx vs greater than pT2 or N+) were assessed with the Kruskal-Wallis and Fisher exact tests as appropriate. Associations between alterations and survival were estimated using the Kaplan-Meier method and Cox regression. RESULTS: Of the 24 most commonly altered genes in 9 pathways TP53/MDM2 alterations and FGFR3 mutations were the only 2 alterations uniformly associated with high grade, advanced stage, nonorgan confined disease, and recurrence-free and cancer specific survival. TP53/MDM2 alterations were associated with adverse clinicopathological outcomes whereas FGFR3 mutations were associated with favorable outcomes. We created a risk score using TP53/MDM2 and FGFR3 status that was able to discriminate between adverse pathological and clinical outcomes, including in the subset of patients with high grade disease. The study is limited by small numbers and lack of validation. CONCLUSIONS: Our data indicate that specific genomic alterations in radical nephroureterectomy specimens correlate with tumor grade, stage and cancer specific survival outcomes.
Source: The Journal of Urology
Authors: Aditya Bagrodia, Eugene K. Cha, John P. Sfakianos, Emily C. Zabor, Bernard H. Bochner, Hikmat A. Al-Ahmadie, David B. Solit, Jonathan A. Coleman, Collaborators S0022534716000331-0ce7e1e518699725ab07c04f3c92fb1c Gopa Iyer, S0022534716000331-2077eb6f085565a64e51c14577d6bc85 Jonathan E. Rosenberg, S0022534716000331-44774fd0209e11ddc2520325fecc817a Dean F. Bajorin, S0022534716000331-48418c391b04c7af17bbc2ba2e67c6f3 Sasinya N. Scott, S0022534716000331-f43b704017af61c80a61be49bb24cc3f Ronak Shah, S0022534716000331-8d98cdeb21395cff027bf6db5a3f79c2 Neil B. Desai, S0022534716000331-688250fc936f2ef00920795681da6123 Byron Lee, S0022534716000331-be9f
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Cancer Institute
OpenAlex ID: W2233492443