Comparative Genomic Landscape of Urothelial Carcinoma of the Bladder Among Patients of East and South Asian Genomic Ancestry

• Published in: The oncologist (Dayton, Ohio) Ohio), 2023-10, Vol.28 (10), p.e910-e920
• Main Authors: Peak, Taylor, Spiess, Philippe E, Li, Roger, Grivas, Petros, Necchi, Andrea, Pavlick, Dean, Huang, Richard S P, Lin, Douglas, Danziger, Natalie, Jacob, Joseph M, Bratslavsky, Gennady, Ross, Jeffrey S
• Format: Article
• Language: English
• Subjects: Analysis; Bladder cancer; Care and treatment; Diagnosis; Gene mutations; Genetic aspects; Genetic variation; Genitourinary Cancer; Health aspects; Smoking
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyad120

Abstract Background Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort. Methods Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a 324-gene hybrid-capture-based method which also calculates tumor mutational burden (TMB) and determines microsatellite status (MSI). Results Of the cohort, 7447 (85.3%) were EUR, 541 (6.2%) were AFR, 461 (5.3%) were of AMR, 74 (0.85%) were SAS, and 205 (2.3%) were EAS. When compared with EUR, TERT GAs were less frequent in SAS (58.1% vs. 73.6%; P = .06). When compared with non-SAS, SAS had less frequent GAs in FGFR3 (9.5% vs. 18.5%, P = .25). TERT promoter mutations were significantly less frequent in EAS compared to non-EAS (54.1% vs. 72.9%; P < .001). When compared with the non-EAS, PIK3CA alterations were significantly less common in EAS (12.7% vs. 22.1%, P = .005). The mean TMB was significantly lower in EAS vs. non-EAS (8.53 vs. 10.02; P = .05). Conclusions The results from this comprehensive genomic analysis of UCB provide important insight into the possible differences in the genomic landscape in a population level. These hypothesis-generating findings require external validation and should support the inclusion of more diverse patient populations in clinical trials. This article presents a comprehensive genomic profiling study of urothelial carcinoma in patients of East and South Asian ancestry, focusing on the identification of frequent and potentially targetable genomic alterations.