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Objective  Bladder urothelial carcinoma (BUC) is a common urological malignancy with molecular heterogeneity. However, the genetic feature of Chinese BUC patients is still not well-identified.    Methods  We performed deep sequencing by a large panel (450 genes) on 22 BUC samples and using matched normal bladder tissue as control. Genomic alterations (GAs), pathways and Tumor Mutation Burden (TMB) were investigated.    Results  The frequencies of GAs ( TERT , 54.5%;  CREBBP , 27.3%;  GATA3 , 22.7%;  BRAF , 18.2%;  TEK , 18.2% and  GLI1 , 18.2%) were significantly higher in Chinese than Western BUC patients. Other GAs’ frequencies were in accordance with previous study ( TP53 , 50.0%;  KDM6A , 31.8%;  KMT2D , 22.7%; etc.). Besides, we detected gene amplification in  ERBB2, FRS2, FAS , etc. The gene fusion/rearrangement took place in the chromosome 11, 12, 14, 17, 19, 22, and Y. Other than cell cycle and PI3K-AKT-mTOR, mutated genes were more associated with the transcription factor, chromatin modification signaling pathways. Interestingly, the TMB value was significantly higher in the BUC patients at stages T1–T2 than T3–T4 ( P  = 0.025).    Conclusion  Deep genomic sequencing of BUC can provide new clues on the unique GAs of Chinese patients and assist in therapeutic decision.

Deep Genomic Sequencing of Bladder Urothelial Carcinoma in Southern Chinese Patients: A Single-Center Study