Objective: Bladder cancer and renal cancer are common malignancies in the urological system.The aims of the present study are to detect the genomic changes in the cancer tissues by massively parallel DNA sequence technology.Methods: The cancer tissues with matched morphologically normal tissues and peripheral blood samples were collected from the patients with urothelial bladder carcinoma(UBC)and clear cell renal cell carcinoma(ccRCC).Whole genome,exome or transcriptome of the samples were sequenced by massively parallel DNA sequencing technology.The somatic mutations,copy number variations and mRNA variations were identified by different bioinformatic methods and validated by Sanger DNA sequencing.Results: We sequenced the exomes of nine individuals with UBC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with UBC with different tumor stages and grades,and identified genetic aberrations of the chromatin remodeling genes(UTX,MLLMLL3,CREBBP-EP300,NCOR1,ARID1A and CHD6)in 59%of our 97 subjects with UBC.Of these genes,we showed UTX to be altered substantially more frequently in tumors of low stages and grades,highlighting its potential role in the classification and diagnosis of bladder cancer.We sequenced whole exomes of 10 ccRCC samples and performed a screen of 1,100 genes in 88 additional ccRCCs,from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC.Notably,we detected frequent mutations in the ubiquitin-mediated proteolysis pathway(UMPP),and alterations in the UMPP were significandy associated with overexpression of HIF1α and HIF2α in the tumors.Conclusions: Our results provide an overview of the genetic basis of UBC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.