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Mutational Patterns In Chemotherapy Resistant Muscle-Invasive Bladder Cancer., David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y.T. Chen, R. Katherine Alpaugh, Jean Hoffman-Censits, Levi A. Garraway, Gad Getz, Scott L. Carter, Joaquim Bellmunt, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen

Department of Medical Oncology Faculty Papers

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts …