Presentation Authors: Aleksandra Walasek*, Bret Wankel, Nima Almassi, Min Yuen Teo, Samuel Funt, Nikolaus Schultz, Guido Dalbagni, Wenhu Hu, Hikmat Al-Ahmadie, Helena Furberg-Barnes, Stacey Petruzella, Dean Bajorin, Jonathan Rosenberg, Gopakumar Iyer, Bernard Bochner, David Solit, Eugene Pietzak, New York, NY
Introduction: Smoking is an important risk factor that is highly associated with development of bladder cancer. There is data suggesting that mutational signatures differ between smoking-related and non-smoking-related cancers. Hypothesizing that genomic alterations differ between smokers and non-smokers who develop bladder cancer, we evaluated for differences in genomic alterations in commonly altered cancer-associated genes using next-generation sequencing.
Methods: All patients with urothelial carcinoma (UC) with tumors that underwent next-generation sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified from our prospectively-maintained institutional database. A panel of genes demonstrated by The Cancer Genome Atlas (TCGA) as being commonly mutated in bladder cancer was selected for analysis.
Results: A total of 1044 samples from 968 patients met the inclusion criteria. Two hundred fifty-nine (25%) of the samples represented upper tract tumors and 785 (75%) represented tumors originating in the bladder. Smokers, active or former, comprised 66% of the cohort. The most frequently mutated 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: In this large cohort of UC patients undergoing next-generation sequencing, we observed a high incidence of genomic alterations consistent with prior studies, with no difference in the incidence of genomic alterations between smokers and non-smokers. We are currently examining smoking-related mutational signatures and differences in genomic alterations as a function of smoking intensity exposure to further explore these effects.
Source of Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Michael and Zena Wiener for Therapeutics Program in Bladder Cancer, Pin Down Bladder Cancer, Cycle for Survival, the Marie-Josee and Henry R. Kravis Center for Mole