Abstract B20: Characterization of tumor mutational landscape in smokers and nonsmokers with urothelial carcinoma

Abstract

Abstract Introduction and Objectives: Smoking is a major risk factor for development of bladder cancer. It has been previously shown that smoking-related and non-smoking-related cancers have characteristic mutational signatures. Hypothesizing that somatic alterations differ between smokers and nonsmokers with urothelial carcinoma, we used next-generation sequencing to evaluate for differences in genomic alterations between these two groups of patients. Methods: We identified in our prospectively maintained institutional database all patients with urothelial carcinoma whose tumors underwent next-generation sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. A panel of genes previously reported by The Cancer Genome Atlas (TCGA) as being commonly mutated in bladder cancer was chosen for analysis. Results: A total of 1,044 samples from 968 patients were included in the analysis. Seven hundred eighty-five (85%) of the samples represented bladder tumors and 259 (25%) of the samples represented tumors of the upper tract. Patients with smoking history comprised 66% of the cohort. The most frequently altered genes in active or former smokers and never smokers were TERT promoter (55% and 60%), TP53 (43% and 41%), KDM6A (30% and 26%), and FGFR3 (27% and 26%). Conclusions: Mutational profiling of urothelial tumors in this large cohort of patients showed high incidence of genomic alterations consistent with prior studies. The frequency of alterations in these genes was similar between smokers and nonsmokers. To further understand smoking-related mutational process, we are examining mutational signatures and differences in genomic alterations as a function of smoking intensity exposure. Citation Format: Aleksandra Walasek, Nima Almassi, Min Yuen Teo, Samuel Funt, Nikolaus Schultz, Guido Dalbagni, Wenhu Hu, Hikmat Al-Ahmadie, Dean F Bajorin, Jonathan E Rosenberg, Gopakumar Iyer, Bernard H. Bochner, David B. Solit, Eugene J. Pietzak. Characterization of tumor mutational landscape in smokers and nonsmokers with urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B20.