Generating a neoantigen map of advanced urothelial carcinoma by whole exome sequencing.

354 Background: immune-checkpoint blockade is a promising treatment of advanced urothelial carcinoma (UC) that unleashes pre-existing immune responses against recognized tumor antigens. Somatic mutations lead to the formation of neoantigens, which are highly antigenic mutant proteins. Methods: Our objective was to generate a neoantigen map through analysis of whole exome sequencing data of our cohort of patients (pts) with platinum-resistant UC. Whole exome sequencing (WES) data from 73 prospectively collected UC samples from 34 patients were analyzed using our neoantigen prediction pipeline. We defined neoantigens as mutant nonamers with high affinity binding to predicted class I MHC molecules for each patient. HLA haplotypes were inferred from WES of matched germline DNA. Results: A significant correlation between global somatic mutation rates, and neo-epitope burden was observed (R2 = 0.93), a similar correlation was observed between single nucleotide variants (SNV) and neo-epitope burdens (R2 = 0.94)....