Comprehensive Genetic Profile of Chinese Muscle-Invasive Bladder Cancer Cohort

Objective: The aim of our study was to characterize the spectrum of mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and exploring potential therapeutic targets.

Methods: We collected samples from 62 Chinese patients with MIBC. For each patient, tumor tissues or blood samples were collected and sequenced by whole exome sequencing.

Results: Our findings revealed the most frequently mutated genes included TP53 (41%), TTN (41%), HYDIN (34%), FRG1 (33%), ZNF717 (23%), AHNAK2 (21%), MUC4 (21%), KMT2D (20%), CDC27 (18%) and IGSF3 (18%). The most frequently mutated DNA damage repair (DDR) genes were TP53 (49%), SMARCA4 (10%), ERCC2 (8%), BRAC2 (6%), HERC2 (6%), HLTF (6%), PALB2 (6%) and POLG (6%). Additionally, our analysis confirmed an association between DDR mutations and high TMB (P = .022). Significant differences in MSI were observed between smokers and nonsmokers (P = .022), drinkers and nondrinkers (P = .018). By analyzing the data of 323 white MIBC samples from TCGA database, we identified frequently mutated driver genes in both our cohort and TCGA white cohort, including TP53, KMT2D, KMT2C, and FGFR3. Our study also revealed genes with distinct mutation frequencies compared to the TCGA white cohort, including FRG1, CDC27, IGSF3, MUC16, and ARID1A.

Conclusions: Our study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications.